U.S. patent application number 12/742840 was filed with the patent office on 2010-12-23 for herbicidal compounds.
This patent application is currently assigned to SYNGENTA CROP PROTECTION, INC.. Invention is credited to Matthew Robert Cordingley, Patrick Jelf Crowley, Suzanna Jane Riley, Michael Drysdale Turnbull, Nigel James Willetts.
Application Number | 20100323889 12/742840 |
Document ID | / |
Family ID | 38896394 |
Filed Date | 2010-12-23 |
United States Patent
Application |
20100323889 |
Kind Code |
A1 |
Willetts; Nigel James ; et
al. |
December 23, 2010 |
HERBICIDAL COMPOUNDS
Abstract
The present invention relates to compounds of formula (I),
wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are as
defined in claim 1; or a salt or N-oxide thereof. Furthermore, the
present invention relates to processes for preparing compounds of
formula (I), to intermediates used in the preparation of compounds
of formula (I), to methods of controlling plants and compositions
comprising compounds of formula (I). ##STR00001##
Inventors: |
Willetts; Nigel James;
(Bracknell, GB) ; Cordingley; Matthew Robert;
(Bracknell, GB) ; Crowley; Patrick Jelf;
(Bracknell, GB) ; Riley; Suzanna Jane; (Bracknell,
GB) ; Turnbull; Michael Drysdale; (Bracknell,
GB) |
Correspondence
Address: |
SYNGENTA CROP PROTECTION , INC.;PATENT AND TRADEMARK DEPARTMENT
410 SWING ROAD
GREENSBORO
NC
27409
US
|
Assignee: |
SYNGENTA CROP PROTECTION,
INC.
Greensboro
NC
|
Family ID: |
38896394 |
Appl. No.: |
12/742840 |
Filed: |
November 10, 2008 |
PCT Filed: |
November 10, 2008 |
PCT NO: |
PCT/GB08/03786 |
371 Date: |
August 30, 2010 |
Current U.S.
Class: |
504/103 ;
504/128; 504/221; 544/407; 544/48 |
Current CPC
Class: |
A01N 43/90 20130101;
C07D 241/26 20130101; C07D 513/04 20130101 |
Class at
Publication: |
504/103 ;
544/407; 544/48; 504/221; 504/128 |
International
Class: |
A01N 57/20 20060101
A01N057/20; C07D 241/26 20060101 C07D241/26; C07D 513/04 20060101
C07D513/04; A01N 43/90 20060101 A01N043/90; A01P 13/00 20060101
A01P013/00; A01N 25/32 20060101 A01N025/32 |
Foreign Application Data
Date |
Code |
Application Number |
Nov 15, 2007 |
GB |
0722472.8 |
Claims
1. A compound of formula (I) ##STR00063## wherein R.sup.1 and
R.sup.2 are independently hydrogen, C.sub.1-C.sub.4alkyl,
C.sub.1-C.sub.4haloalkyl, halo, cyano, hydroxy,
C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4alkylthio, aryl or aryl
substituted by one to five R.sup.6, which may be the same or
different, or heteroaryl or heteroaryl substituted by one to five
R.sup.6, which may be the same or different; R.sup.3 is hydrogen,
C.sub.1-C.sub.10alkyl, C.sub.1-C.sub.4haloalkyl,
C.sub.2-C.sub.10alkenyl, C.sub.2-C.sub.4haloalkenyl,
C.sub.2-C.sub.10alkynyl, C.sub.2-C.sub.4haloalkynyl,
C.sub.3-C.sub.10cycloalkyl,
C.sub.3-C.sub.10cycloalkyl-C.sub.1-C.sub.6alkyl-,
C.sub.1-C.sub.10alkoxy-C.sub.1-C.sub.6alkyl-,
C.sub.1-C.sub.10cyanoalkyl-,
C.sub.1-C.sub.10alkoxycarbonyl-C.sub.1-C.sub.6alkyl-,
N--C.sub.1-C.sub.3alkyl-aminocarbonyl-C.sub.1-C.sub.6alkyl-,
N,N-di-(C.sub.1-C.sub.3alkyl)-aminocarbonyl-C.sub.1-C.sub.6alkyl-,
aryl-C.sub.1-C.sub.6alkyl- or aryl-C.sub.1-C.sub.6alkyl- wherein
the aryl moiety is substituted by one to three R.sup.7, which may
be the same or different, or heterocyclyl-C.sub.1-C.sub.6alkyl- or
heterocyclyl-C.sub.1-C.sub.6alkyl- wherein the heterocyclyl moiety
is substituted by one to three R.sup.7, which may be the same or
different; R.sup.4 is aryl or aryl substituted by one to five
R.sup.8, which may be the same or different, or heteroaryl or
heteroaryl substituted by one to four R.sup.8, which may be the
same or different; R.sup.5 is hydroxy or a group which can be
metabolized to a hydroxy group; each R.sup.6, R.sup.7 and R.sup.8
is independently halo, cyano, nitro, C.sub.1-C.sub.10alkyl,
C.sub.1-C.sub.4haloalkyl, C.sub.2-C.sub.10alkenyl,
C.sub.2-C.sub.10alkynyl, hydroxy, C.sub.1-C.sub.10alkoxy,
C.sub.1-C.sub.4haloalkoxy,
C.sub.1-C.sub.10alkoxy-C.sub.1-C.sub.4alkyl-,
C.sub.3-C.sub.7cycloalkyl, C.sub.3-C.sub.7cycloalkoxy,
C.sub.3-C.sub.7cycloalkyl-C.sub.1-C.sub.4alkyl-,
C.sub.3-C.sub.7cycloalkyl-C.sub.1-C.sub.4alkoxy-,
C.sub.1-C.sub.6alkylcarbonyl-, formyl,
C.sub.1-C.sub.4alkoxycarbonyl-, C.sub.1-C.sub.4alkylcarbonyloxy-,
C.sub.1-C.sub.10alkylthio-, C.sub.1-C.sub.4haloalkylthio-,
C.sub.1-C.sub.10alkylsulfinyl-, C.sub.1-C.sub.4haloalkylsulfinyl-,
C.sub.1-C.sub.10alkylsulfonyl-, C.sub.1-C.sub.4haloalkylsulfonyl-,
amino, C.sub.1-C.sub.10alkylamino-, di-C.sub.1-C.sub.10alkylamino-,
C.sub.1-C.sub.10alkylcarbonylamino-, aryl or aryl substituted by
one to three R.sup.13, which may be the same or different,
heteroaryl or heteroaryl substituted by one to three R.sup.13,
which may be the same or different, aryl-C.sub.1-C.sub.4alkyl- or
aryl-C.sub.1-C.sub.4alkyl- wherein the aryl moiety is substituted
by one to three R.sup.13, which may be the same or different,
heteroaryl-C.sub.1-C.sub.4alkyl- or
heteroaryl-C.sub.1-C.sub.4alkyl- wherein the heteroaryl moiety is
substituted by one to three R.sup.13, which may be the same or
different, aryloxy- or aryloxy-substituted by one to three
R.sup.13, which may be the same or different, heteroaryloxy- or
heteroaryloxy-substituted by one to three R.sup.13, which may be
the same or different, arylthio- or arylthio-substituted by one to
three R.sup.13, which may be the same or different, or
heteroarylthio- or heteroarylthio-substituted by one to three
R.sup.13, which may be the same or different; and each R.sup.13 is
independently halo, cyano, nitro, C.sub.1-C.sub.6alkyl,
C.sub.1-C.sub.6haloalkyl or C.sub.1-C.sub.6alkoxy; or a salt or
N-oxide thereof.
2. A compound according to claim 1 wherein R.sup.1 is hydrogen,
C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, halo, cyano,
hydroxy or C.sub.1-C.sub.4alkoxy.
3. A compound according to claim 1 or claim 2 wherein R.sup.2 is
hydrogen, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, halo,
cyano, hydroxy or C.sub.1-C.sub.4alkoxy.
4. A compound according to claim 1 wherein R.sup.3 is hydrogen,
C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl,
C.sub.2-C.sub.4alkenyl, C.sub.2-C.sub.4haloalkenyl,
C.sub.2-C.sub.4alkynyl or C.sub.2-C.sub.4haloalkynyl.
5. A compound according to claim 1 wherein R.sup.4 is aryl or aryl
substituted by one to five R.sup.8, which may be the same or
different.
6. A compound according to claim 1 wherein R.sup.5 is hydroxy,
R.sup.9-oxy-, R.sup.10-carbonyloxy-, tri-R.sup.11-silyloxy- or
R.sup.12-sulfonyloxy-, wherein R.sup.9 is C.sub.1-C.sub.10alkyl,
C.sub.2-C.sub.10alkenyl, C.sub.2-C.sub.10alkynyl or
aryl-C.sub.1-C.sub.4alkyl- or aryl-C.sub.1-C.sub.4alkyl- wherein
the aryl moiety is substituted by one to five substituents
independently selected from halo, cyano, nitro,
C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl or
C.sub.1-C.sub.6alkoxy; R.sup.10 is C.sub.1-C.sub.10alkyl,
C.sub.3-C.sub.10cycloalkyl,
C.sub.3-C.sub.10cycloalkyl-C.sub.1-C.sub.10alkyl-,
C.sub.1-C.sub.10haloalkyl, C.sub.2-C.sub.10alkenyl,
C.sub.2-C.sub.10alkynyl,
C.sub.1-C.sub.4alkoxy-C.sub.1-C.sub.10alkyl-,
C.sub.1-C.sub.4alkylthio-C.sub.1-C.sub.4alkyl-,
C.sub.1-C.sub.10alkoxy, C.sub.2-C.sub.10alkenyloxy,
C.sub.2-C.sub.10alkynyloxy, C.sub.1-C.sub.10alkylthio-,
N,N-di-(C.sub.1-C.sub.4alkyl)-amino-, aryl or aryl substituted by
one to three R.sup.14, which may be the same or different,
heteroaryl or heteroaryl substituted by one to three R.sup.14,
which may be the same or different, aryl-C.sub.1-C.sub.4alkyl- or
aryl-C.sub.1-C.sub.4alkyl- wherein the aryl moiety is substituted
by one to three R.sup.14, which may be the same or different,
heteroaryl-C.sub.1-C.sub.4alkyl- or
heteroaryl-C.sub.1-C.sub.4alkyl- wherein the heteroaryl moiety is
substituted by one to three R.sup.14, which may be the same or
different, aryloxy- or aryloxy-substituted by one to three
R.sup.14, which may be the same or different, heteroaryloxy- or
heteroaryloxy-substituted by one to three R.sup.14, which may be
the same or different, arylthio- or arylthio-substituted by one to
three R.sup.14, which may be the same or different, or
heteroarylthio- or heteroarylthio-substituted by one to three
R.sup.14, which may be the same or different; each R.sup.11 is
independently C.sub.1-C.sub.10alkyl or phenyl or phenyl substituted
by one to five substituents independently selected from halo,
cyano, nitro, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl or
C.sub.1-C.sub.6alkoxy; R.sup.12 is C.sub.1-C.sub.10alkyl,
C.sub.1-C.sub.10haloalkyl, or phenyl or phenyl substituted by one
to five substituents independently selected from halo, cyano,
nitro, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl or
C.sub.1-C.sub.6alkoxy; and each R.sup.14 is independently halo,
cyano, nitro, C.sub.1-C.sub.10alkyl, C.sub.1-C.sub.4haloalkyl,
C.sub.1-C.sub.10alkoxy, C.sub.1-C.sub.4alkoxycarbonyl-,
C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.10alkylthio-,
C.sub.1-C.sub.4haloalkylthio-, C.sub.1-C.sub.10alkylsulfinyl-,
C.sub.1-C.sub.4haloalkylsulfinyl-, C.sub.1-C.sub.10alkylsulfonyl-,
C.sub.1-C.sub.4haloalkylsulfonyl-, aryl or aryl substituted by one
to five substituents independently selected from halo, cyano,
nitro, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl or
C.sub.1-C.sub.6alkoxy, or heteroaryl or heteroaryl substituted by
one to four substituents independently selected from halo, cyano,
nitro, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl or
C.sub.1-C.sub.6alkoxy.
7. A compound of formula (J) ##STR00064## wherein R.sup.1, R.sup.2,
and R.sup.4 are as defined in claim 1; and R.sup.16 is
C.sub.1-C.sub.6alkyl; or a salt or N-oxide thereof.
8. Another group are compounds of formula (K) ##STR00065## wherein
R.sup.1, R.sup.2, and R.sup.4 are as defined in claim 1; R.sup.3 is
C.sub.1-C.sub.10alkyl, C.sub.2-C.sub.10alkenyl,
C.sub.2-C.sub.10alkynyl, C.sub.3-C.sub.10cycloalkyl,
C.sub.3-C.sub.10cycloalkyl-C.sub.1-C.sub.6alkyl-,
C.sub.1-C.sub.10alkoxy-C.sub.1-C.sub.6alkyl-,
C.sub.1-C.sub.10cyanoalkyl-,
C.sub.1-C.sub.10alkoxycarbonyl-C.sub.1-C.sub.6alkyl-,
N--C.sub.1-C.sub.3alkyl-aminocarbonyl-C.sub.1-C.sub.6alkyl-,
N,N-di-(C.sub.1-C.sub.3alkyl)-aminocarbonyl-C.sub.1-C.sub.6alkyl-,
aryl-C.sub.1-C.sub.6alkyl- or aryl-C.sub.1-C.sub.6alkyl- wherein
the aryl moiety is substituted by one to three R.sup.7, which may
be the same or different, or heterocyclyl-C.sub.1-C.sub.6alkyl- or
heterocyclyl-C.sub.1-C.sub.6alkyl- wherein the heterocyclyl moiety
is substituted by one to three R.sup.7, which may be the same or
different; and R.sup.16 is C.sub.1-C.sub.6alkyl; or a salt or
N-oxide thereof.
9. A method of controlling plants which comprises applying to the
plants or to the locus thereof a herbicidally effective amount of a
compound of formula (I) as defined in claim 1.
10. A herbicidal composition which comprises a herbicidally
effective amount of a compound of formula (I) as defined in claim 1
in addition to formulation adjuvants.
11. A herbicidal composition which comprises a herbicidally
effective amount of a compound of formula (I) as defined in claim
1, optionally one or more further herbicides, and optionally one or
more safeners.
Description
[0001] The present invention relates to novel herbicidal
1H-2-thia-1,5,8-triaza-naphthalene-2,2-dioxides, to processes for
their preparation, to intermediates used in the preparation of such
compounds, to compositions comprising those compounds, and to their
use in controlling plants or in inhibiting plant growth.
[0002] It has now surprisingly been found that certain
1H-2-thia-1,5,8-triaza-naphthalene-2,2-dioxides display excellent
herbicidal and growth-inhibiting properties.
[0003] The present invention therefore provides a compound of
formula (I)
##STR00002##
wherein R.sup.1 and R.sup.2 are independently hydrogen,
C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, halo, cyano,
hydroxy, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4alkylthio, aryl or
aryl substituted by one to five R.sup.6, which may be the same or
different, or heteroaryl or heteroaryl substituted by one to five
R.sup.6, which may be the same or different; R.sup.3 is hydrogen,
C.sub.1-C.sub.10alkyl, C.sub.1-C.sub.4haloalkyl,
C.sub.2-C.sub.10alkenyl, C.sub.2-C.sub.4haloalkenyl,
C.sub.2-C.sub.10alkynyl, C.sub.2-C.sub.4haloalkynyl,
C.sub.3-C.sub.10cycloalkyl,
C.sub.3-C.sub.10cycloalkyl-C.sub.1-C.sub.6alkyl-,
C.sub.1-C.sub.10alkoxy-C.sub.1-C.sub.6alkyl-,
C.sub.1-C.sub.10cyanoalkyl-,
C.sub.1-C.sub.10alkoxycarbonyl-C.sub.1-C.sub.6alkyl-,
N--C.sub.1-C.sub.3alkyl-aminocarbonyl-C.sub.1-C.sub.6alkyl-,
N,N-di-(C.sub.1-C.sub.3alkyl)-aminocarbonyl-C.sub.1-C.sub.6alkyl-,
aryl-C.sub.1-C.sub.6alkyl- or aryl-C.sub.1-C.sub.6alkyl- wherein
the aryl moiety is substituted by one to three R.sup.7, which may
be the same or different, or heterocyclyl-C.sub.1-C.sub.6alkyl- or
heterocyclyl-C.sub.1-C.sub.6alkyl- wherein the heterocyclyl moiety
is substituted by one to three R.sup.7, which may be the same or
different; R.sup.4 is aryl or aryl substituted by one to five
R.sup.8, which may be the same or different, or heteroaryl or
heteroaryl substituted by one to four R.sup.8, which may be the
same or different; R.sup.5 is hydroxy or a group which can be
metabolized to a hydroxy group; each R.sup.6, R.sup.7 and R.sup.8
is independently halo, cyano, nitro, C.sub.1-C.sub.10alkyl,
C.sub.1-C.sub.4haloalkyl, C.sub.2-C.sub.10alkenyl,
C.sub.2-C.sub.10alkynyl, hydroxy, C.sub.1-C.sub.10alkoxy,
C.sub.1-C.sub.4haloalkoxy,
C.sub.1-C.sub.10alkoxy-C.sub.1-C.sub.4alkyl-,
C.sub.3-C.sub.7cycloalkyl, C.sub.3-C.sub.7cycloalkoxy,
C.sub.3-C.sub.7cycloalkyl-C.sub.1-C.sub.4alkyl-,
C.sub.3-C.sub.7cycloalkyl-C.sub.1-C.sub.4alkoxy-,
C.sub.1-C.sub.6alkylcarbonyl-, formyl,
C.sub.1-C.sub.4alkoxycarbonyl-, C.sub.1-C.sub.4alkylcarbonyloxy-,
C.sub.1-C.sub.10alkylthio-, C.sub.1-C.sub.4haloalkylthio-,
C.sub.1-C.sub.10alkylsulfinyl-, C.sub.1-C.sub.4haloalkylsulfinyl-,
C.sub.1-C.sub.10alkylsulfonyl-, C.sub.1-C.sub.4haloalkylsulfonyl-,
amino, C.sub.r C.sub.10alkylamino-, di-C.sub.1-C.sub.10alkylamino-,
C.sub.1-C.sub.10alkylcarbonylamino-, aryl or aryl substituted by
one to three R.sup.13, which may be the same or different,
heteroaryl or heteroaryl substituted by one to three R.sup.13,
which may be the same or different, aryl-C.sub.1-C.sub.4alkyl- or
aryl-C.sub.1-C.sub.4alkyl- wherein the aryl moiety is substituted
by one to three R.sup.13, which may be the same or different,
heteroaryl-C.sub.1-C.sub.4alkyl- or
heteroaryl-C.sub.1-C.sub.4alkyl- wherein the heteroaryl moiety is
substituted by one to three R.sup.13, which may be the same or
different, aryloxy- or aryloxy-substituted by one to three
R.sup.13, which may be the same or different, heteroaryloxy- or
heteroaryloxy-substituted by one to three R.sup.13, which may be
the same or different, arylthio- or arylthio-substituted by one to
three R.sup.13, which may be the same or different, or
heteroarylthio- or heteroarylthio-substituted by one to three
R.sup.13, which may be the same or different; and each R.sup.13 is
independently halo, cyano, nitro, C.sub.1-C.sub.6alkyl,
C.sub.1-C.sub.6haloalkyl or C.sub.1-C.sub.6alkoxy; or a salt or
N-oxide thereof.
[0004] The compounds of formula (I) may exist in different
geometric or optical isomers or tautomeric forms. This invention
covers all such isomers and tautomers and mixtures thereof in all
proportions as well as isotopic forms such as deuterated compounds.
Furthermore, it is possible that atropisomers are obtained in those
cases where the rotation of the R.sup.4 group is restricted, for
example in those cases where the R.sup.4 group has at least one
ortho-substituent.
[0005] For example, a compound of formula (A), i.e. a compound of
formula (I) wherein R.sup.3 is hydrogen and R.sup.5 is hydroxy, can
be drawn in two tautomeric forms.
##STR00003##
Some of these compounds exhibit good herbicidal activity.
Additionally, these compounds can be used as intermediates for the
synthesis of compounds of the formula (B), (C) and (D).
[0006] For example, a compound of formula (B), i.e. a compound of
formula (I) wherein R.sup.3 is hydrogen and R.sup.5 is as defined
for a compound of formula (I) other than hydroxy, can be drawn in
only one tautomeric form.
##STR00004##
Some of these compounds exhibit good herbicidal activity.
Additionally, these compounds can be used as intermediates for the
synthesis of compounds of the formula (A), (C) and (D).
[0007] A compound of formula (C), i.e. a compound of formula (I)
wherein R.sup.3 is as defined for a compound of formula (I) other
than hydrogen and R.sup.5 is as defined for a compound of formula
(I) other than hydroxy, can be drawn in only one tautomeric
form.
##STR00005##
Most of these compounds exhibit excellent herbicidal activity.
Additionally, these compounds can be used as intermediates for the
synthesis of compounds of the formula (A), (B) and (D).
[0008] A compound of formula (D), i.e. a compound of formula (I)
wherein R.sup.3 is as defined for a compound of formula (I) other
than hydrogen and R.sup.5 is hydroxy, can be drawn in two
tautomeric forms.
##STR00006##
Most of these compounds exhibit good herbicidal activity.
Additionally, these compounds can be used as intermediates for the
synthesis of compounds of the formula (A), (B) and (C).
[0009] Each alkyl moiety (either alone or as part of a larger
group, such as alkoxy, alkoxycarbonyl, alkylcarbonyl,
alkylaminocarbonyl, dialkylaminocarbonyl) is a straight or branched
chain and is, for example, methyl, ethyl, n-propyl, n-butyl,
n-pentyl, n-hexyl, iso-propyl, n-butyl, sec-butyl, iso-butyl,
tert-butyl or neo-pentyl. The alkyl groups are preferably C.sub.1
to C.sub.6 alkyl groups, more preferably C.sub.1-C.sub.4 and most
preferably C.sub.1-C.sub.3 alkyl groups.
[0010] Alkenyl and alkynyl moieties (either alone or as part of a
larger group, such as alkenyloxy or alkynyloxy) can be in the form
of straight or branched chains, and the alkenyl moieties, where
appropriate, can be of either the (E)- or (Z)-configuration.
Examples are vinyl, allyl, prop-2-enyl and propargyl. The alkenyl
and alkynyl groups are preferably C.sub.2 to C.sub.6 alkenyl or
alkynyl groups, more preferably C.sub.2-C.sub.4 and most preferably
C.sub.2-C.sub.3 alkenyl or alkynyl groups.
[0011] Halogen is fluorine, chlorine, bromine or iodine.
[0012] Haloalkyl groups (either alone or as part of a larger group,
such as haloalkoxy or haloalkylthio) are alkyl groups which are
substituted with one or more of the same or different halogen atoms
and are, for example, --CF.sub.3, --CF.sub.2Cl, --CHF.sub.2,
--CH.sub.2CF.sub.3 or --CH.sub.2CHF.sub.2. Haloalkenyl and
haloalkynyl groups (either alone or as part of a larger group, such
as haloalkenyloxy or haloalkynyloxy) are alkenyl and alkynyl
groups, respectively, which are substituted with one or more of the
same or different halogen atoms and are, for example,
--CH.dbd.CF.sub.2, --CCl.dbd.CClF or --C.ident.CCl.
[0013] Cyanoalkyl groups are alkyl groups which are substituted
with one or more cyano groups, for example, cyanomethyl or
1,3-dicyanopropyl.
[0014] Cycloalkyl groups can be in mono- or bi-cyclic form and may
optionally be substituted by one or more methyl groups. The
cycloalkyl groups preferably contain 3 to 8 carbon atoms, more
preferably 3 to 6 carbon atoms. Examples of monocyclic cycloalkyl
groups are cyclopropyl, 1-methylcyclopropyl, 2-methylcyclopropyl,
cyclobutyl, cyclopentyl and cyclohexyl.
[0015] In the context of the present specification the term "aryl"
refers to a ring system which may be mono-, bi- or tricyclic.
Examples of such rings include phenyl, naphthalenyl, anthracenyl,
indenyl or phenanthrenyl. A preferred aryl group is phenyl.
[0016] The term "heteroaryl" refers to an aromatic ring system
containing at least one heteroatom and consisting either of a
single ring or of two or more fused rings. Preferably, single rings
contain up to three heteroatoms and bicyclic systems up to four
heteroatoms which are preferably chosen from nitrogen, oxygen and
sulfur. Examples of monocyclic groups include pyridyl, pyridazinyl,
pyrimidinyl, pyrazinyl, triazinyl, furanyl, thiophenyl, oxazolyl,
isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl,
pyrrolyl, pyrazolyl, imidazolyl, triazolyl and tetrazolyl. A
preferred monocyclic heteroaryl group is pyridyl, such as
3-ethoxycarbonyl-6-trifluoromethyl-pyrid-2-yl. Examples of bicyclic
groups are benzothiophenyl, benzimidazolyl, benzothiadiazolyl,
quinolinyl, cinnolinyl, quinoxalinyl and
pyrazolo[1,5-a]pyrimidinyl. A preferred bicyclic heteroaryl group
is quinolinyl, such as 2-chloro-quinolin-2-yl.
[0017] The term "heterocyclyl" is defined to include heteroaryl and
in addition their unsaturated or partially unsaturated analogues
such as 4,5,6,7-tetrahydro-benzothiophenyl, chromen-4-onyl,
9H-fluorenyl, 3,4-dihydro-2H-benzo-1,4-dioxepinyl,
2,3-dihydro-benzofuranyl, piperidinyl, 1,3-dioxolanyl,
1,3-dioxanyl, 4,5-dihydro-isoxazolyl, tetrahydrofuranyl and
morpholinyl.
[0018] The term "herbicide" as used herein means a compound that
controls or modifies the growth of plants. The term "herbicidally
effective amount" means the quantity of such a compound or
combination of such compounds that is capable of producing a
controlling or modifying effect on the growth of plants.
Controlling or modifying effects include all deviation from natural
development, for example: killing, retardation, leaf burn,
albinism, dwarfing and the like. The term "plants" refers to all
physical parts of a plant, including seeds, seedlings, saplings,
roots, tubers, stems, stalks, foliage, and fruits. The term "locus"
is intended to include soil, seeds, and seedlings, as well as
established vegetation. The term "metabolism" as used herein means
the conversion or breakdown of a substance from one form to another
by a living organism, in particular in a plant (in planta).
[0019] Preferred values of R.sup.1, R.sup.2, R.sup.3, R.sup.4,
R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.11,
R.sup.12, R.sup.13 and R.sup.14 are, in any combination, as set out
below.
[0020] Preferably R.sup.1 is hydrogen, C.sub.1-C.sub.4alkyl,
C.sub.1-C.sub.4haloalkyl, halo, cyano, hydroxy or
C.sub.1-C.sub.4alkoxy, more preferably hydrogen,
C.sub.1-C.sub.4alkyl, halo, cyano or hydroxy, even more preferably
hydrogen, methyl, chloro or bromo, yet even more preferably
hydrogen or chloro, most preferably hydrogen.
[0021] Preferably R.sup.2 is hydrogen, C.sub.1-C.sub.4alkyl,
C.sub.1-C.sub.4haloalkyl, halo, cyano, hydroxy or
C.sub.1-C.sub.4alkoxy, more preferably hydrogen,
C.sub.1-C.sub.4alkyl, halo, cyano or hydroxy, even more preferably
hydrogen, methyl, chloro or bromo, yet even more preferably
hydrogen or chloro, most preferably hydrogen.
[0022] Preferably R.sup.3 is hydrogen, C.sub.1-C.sub.4alkyl,
C.sub.1-C.sub.4haloalkyl, C.sub.2-C.sub.4alkenyl,
C.sub.2-C.sub.4haloalkenyl, C.sub.2-C.sub.4alkynyl or
C.sub.2-C.sub.4haloalkynyl. Examples of such preferred groups for
R.sup.3 are hydrogen, methyl, ethyl, n-propyl, iso-propyl, n-butyl,
2-methyl-propyl, 2-fluoro-ethyl, 2,2-difluoro-ethyl,
2,2,2-trifluoro-ethyl, allyl, but-3-en-1-yl and propargyl.
[0023] More preferably R.sup.3 is hydrogen, C.sub.1-C.sub.2alkyl,
C.sub.1-C.sub.2haloalkyl, C.sub.2-C.sub.3alkenyl or
C.sub.2-C.sub.3alkynyl. Examples of such more preferred groups for
R.sup.3 are hydrogen, methyl, ethyl, 2,2-difluoro-ethyl,
2,2,2-trifluoro-ethyl, allyl and propargyl.
[0024] Most preferably R.sup.3 is hydrogen, C.sub.1-C.sub.2alkyl,
C.sub.1-C.sub.2haloalkyl or C.sub.2-C.sub.3alkynyl. Examples of
such most preferred groups for R.sup.3 are hydrogen, methyl, ethyl,
2,2-difluoro-ethyl and propargyl.
[0025] Preferably R.sup.4 is aryl or aryl substituted by one to
five R.sup.8, which may be the same or different, more preferably
R.sup.4 is aryl substituted by one to four R.sup.8, which may be
the same or different, most preferably R.sup.4 is aryl substituted
by two to three R.sup.8, which may be the same or different.
[0026] In one preferred embodiment R.sup.4 is
2,5-bis-(trifluoromethyl)-phenyl.
[0027] In one preferred embodiment R.sup.4 is
3-bromo-2-chloro-6-fluoro-phenyl.
[0028] In one preferred embodiment R.sup.4 is
4-bromo-2-trifluoromethyl-phenyl.
[0029] In one preferred embodiment R.sup.4 is
2-chloro-3,6-difluoro-phenyl.
[0030] In one preferred embodiment R.sup.4 is
2-chloro-5-fluoro-phenyl.
[0031] In one preferred embodiment R.sup.4 is
2-chloro-5-trifluoromethyl-phenyl.
[0032] In one preferred embodiment R.sup.4 is
2-chloro-6-trifluoromethyl-phenyl.
[0033] In one preferred embodiment R.sup.4 is
4-chloro-2-trifluoromethyl-phenyl.
[0034] In one preferred embodiment R.sup.4 is
5-chloro-2-trifluoromethyl-phenyl.
[0035] In one preferred embodiment R.sup.4 is
2,3-dichloro-6-fluoro-phenyl.
[0036] In one preferred embodiment R.sup.4 is
2,6-dichloro-phenyl.
[0037] In one preferred embodiment R.sup.4 is
2,6-dichloro-4-trifluoromethoxy-phenyl.
[0038] In one preferred embodiment R.sup.4 is 2-iodo-phenyl.
[0039] In one preferred embodiment R.sup.4 is
2,3,6-trichloro-phenyl.
[0040] Preferably R.sup.5 is hydroxy, R.sup.9-oxy-,
R.sup.10-carbonyloxy-, tri-R.sup.11-silyloxy- or
R.sup.12-sulfonyloxy-, wherein
R.sup.9 is C.sub.1-C.sub.10alkyl, C.sub.2-C.sub.10alkenyl,
C.sub.2-C.sub.10alkynyl or aryl-C.sub.1-C.sub.4alkyl- or
aryl-C.sub.1-C.sub.4alkyl- wherein the aryl moiety is substituted
by one to five substituents independently selected from halo,
cyano, nitro, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl or
C.sub.1-C.sub.6alkoxy; R.sup.10 is C.sub.1-C.sub.10alkyl,
C.sub.3-C.sub.10cycloalkyl,
C.sub.3-C.sub.10cycloalkyl-C.sub.1-C.sub.10alkyl-,
C.sub.1-C.sub.10haloalkyl, C.sub.2-C.sub.10alkenyl,
C.sub.2-C.sub.10alkynyl,
C.sub.1-C.sub.4alkoxy-C.sub.1-C.sub.10alkyl-,
C.sub.1-C.sub.4alkylthio-C.sub.1-C.sub.4alkyl-,
C.sub.1-C.sub.10alkoxy, C.sub.2-C.sub.10alkenyloxy,
C.sub.2-C.sub.10alkynyloxy, C.sub.1-C.sub.10alkylthio-,
N--C.sub.1-C.sub.4alkyl-amino-,
N,N-di-(C.sub.1-C.sub.4alkyl)-amino-, aryl or aryl substituted by
one to three R.sup.14, which may be the same or different,
heteroaryl or heteroaryl substituted by one to three R.sup.14,
which may be the same or different, aryl-C.sub.1-C.sub.4alkyl- or
aryl-C.sub.1-C.sub.4alkyl- wherein the aryl moiety is substituted
by one to three R.sup.14, which may be the same or different,
heteroaryl-C.sub.1-C.sub.4alkyl- or
heteroaryl-C.sub.1-C.sub.4alkyl- wherein the heteroaryl moiety is
substituted by one to three R.sup.14, which may be the same or
different, aryloxy- or aryloxy-substituted by one to three
R.sup.14, which may be the same or different, heteroaryloxy- or
heteroaryloxy-substituted by one to three R.sup.14, which may be
the same or different, arylthio- or arylthio-substituted by one to
three R.sup.14, which may be the same or different, or
heteroarylthio- or heteroarylthio-substituted by one to three
R.sup.14, which may be the same or different; each R.sup.11 is
independently C.sub.1-C.sub.10alkyl or phenyl or phenyl substituted
by one to five substituents independently selected from halo,
cyano, nitro, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl or
C.sub.1-C.sub.6alkoxy; R.sup.12 is C.sub.1-C.sub.10alkyl,
C.sub.1-C.sub.10haloalkyl, or phenyl or phenyl substituted by one
to five substituents independently selected from halo, cyano,
nitro, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl or
C.sub.1-C.sub.6alkoxy; and each R.sup.14 is independently halo,
cyano, nitro, C.sub.1-C.sub.10alkyl, C.sub.1-C.sub.4haloalkyl,
C.sub.1-C.sub.10alkoxy, C.sub.1-C.sub.4alkoxycarbonyl-,
C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.10alkylthio-,
C.sub.1-C.sub.4haloalkylthio-, C.sub.1-C.sub.10alkylsulfinyl-,
C.sub.1-C.sub.4haloalkylsulfinyl-, C.sub.1-C.sub.10alkylsulfonyl-,
C.sub.1-C.sub.4haloalkylsulfonyl-, aryl or aryl substituted by one
to five substituents independently selected from halo, cyano,
nitro, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl or
C.sub.1-C.sub.6alkoxy, or heteroaryl or heteroaryl substituted by
one to four substituents independently selected from halo, cyano,
nitro, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl or
C.sub.1-C.sub.6alkoxy.
[0041] More preferably R.sup.5 is hydroxy, R.sup.9-oxy- or
R.sup.10-carbonyloxy-.
[0042] Even more preferably R.sup.5 is hydroxy,
C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4alkenyloxy,
C.sub.1-C.sub.4alkynyloxy, aryl-C.sub.1-C.sub.4alkoxy or
aryl-C.sub.1-C.sub.4alkoxy wherein the aryl moiety is substituted
by one to three R.sup.14, which may be the same or different,
heteroaryl-C.sub.1-C.sub.4alkoxy or
heteroaryl-C.sub.1-C.sub.4alkoxy wherein the heteroaryl moiety is
substituted by one to three R.sup.14, which may be the same or
different, C.sub.1-C.sub.4alkylcarbonyloxy-,
C.sub.3-C.sub.6cyclo-alkylcarbonyloxy-,
C.sub.3-C.sub.10cycloalkyl-C.sub.1-C.sub.10alkylcarbonyloxy-,
C.sub.1-C.sub.4haloalkylcarbonyl-oxy-,
C.sub.2-C.sub.4alkenylcarbonyloxy-,
C.sub.2-C.sub.4alkenylcarbonyloxy-,
C.sub.1-C.sub.4alkoxy-C.sub.1-C.sub.4alkyl-carbonyloxy-,
C.sub.1-C.sub.4alkylthio-C.sub.1-C.sub.4alkylcarbonyloxy-,
C.sub.1-C.sub.4alkoxycarbonyloxy-,
C.sub.2-C.sub.4alkenyloxycarbonyloxy-,
C.sub.2-C.sub.4alkenyloxycarbonyloxy-,
C.sub.1-C.sub.4alkylthiocarbonyloxy-,
N--C.sub.1-C.sub.4alkyl-aminocarbonyloxy-,
N,N-di-(C.sub.1-C.sub.4alkyl)-aminocarbonyloxy-, aryl-carbonyloxy-
or arylcarbonyloxy-substituted by one to three R.sup.14, which may
be the same or different, heteroarylcarbonyloxy- or
heteroarylcarbonyloxy-substituted by one to three R.sup.14, which
may be the same or different, aryl-C.sub.1-C.sub.4alkylcarbonyloxy-
or aryl-C.sub.1-C.sub.4alkylcarbonyloxy- wherein the aryl moiety is
substituted by one to three R.sup.14, which may be the same or
different, heteroaryl-C.sub.1-C.sub.4alkylcarbonyloxy- or
heteroaryl-C.sub.1-C.sub.4alkylcarbonyloxy- wherein the heteroaryl
moiety is substituted by one to three R.sup.14, which may be the
same or different, aryloxycarbonyloxy- or
aryloxycarbonyloxy-substituted by one to three R.sup.14, which may
be the same or different, heteroaryloxy-carbonyloxy- or
heteroaryloxycarbonyloxy-substituted by one to three R.sup.14,
which may be the same or different, arylthiocarbonyloxy- or
arylthiocarbonyloxy-substituted by one to three R.sup.14, which may
be the same or different, or heteroarylthiocarbonyloxy- or
heteroarylthiocarbonyloxy-substituted by one to three R.sup.14,
which may be the same or different.
[0043] Yet even more preferably R.sup.5 is hydroxy,
C.sub.1-C.sub.4alkylcarbonyloxy-,
C.sub.3-C.sub.6cyclo-alkylcarbonyloxy-,
C.sub.2-C.sub.4alkenylcarbonyloxy-,
C.sub.2-C.sub.4alkynylcarbonyloxy-,
C.sub.1-C.sub.4alkoxycarbonyloxy-,
C.sub.2-C.sub.4alkenyloxycarbonyloxy-,
C.sub.2-C.sub.4alkynyloxycarbonyloxy- or
C.sub.1-C.sub.4alkylthiocarbonyloxy-.
[0044] Most preferably R.sup.5 is hydroxy,
C.sub.1-C.sub.4alkylcarbonyloxy-, C.sub.1-C.sub.4alkoxycarbonyloxy-
or C.sub.1-C.sub.4alkylthiocarbonyloxy-. Examples of most preferred
groups for R.sup.5 are hydroxy, methylcarbonyloxy-,
ethylcarbonyloxy-, iso-propylcarbonyloxy-, n-propyl-carbonyloxy-,
but-2-ylcarbonyloxy-, 2-methyl-propylcarbonyloxy-,
tert-butylcarbonyl-oxy-, ethoxycarbonyloxy-, and
ethylthiocarbonyloxy-.
[0045] in one preferred embodiment R.sup.5 is hydroxy.
[0046] In one preferred embodiment R.sup.5 is R.sup.9-oxy-, wherein
R.sup.9 is C.sub.1-C.sub.10alkyl, C.sub.2-C.sub.10alkenyl,
C.sub.2-C.sub.10alkynyl or aryl-C.sub.1-C.sub.4alkyl- or
aryl-C.sub.1-C.sub.4alkyl- wherein the aryl moiety is substituted
by one to five substituents independently selected from halo,
cyano, nitro, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl or
C.sub.1-C.sub.6alkoxy. Such R.sup.5 groups may be metabolized,
preferably in planta, to give the corresponding compound wherein
R.sup.5 is hydroxy.
[0047] In one preferred embodiment R.sup.5 is
R.sup.10-carbonyloxy-, wherein R.sup.10 is C.sub.1-C.sub.10alkyl,
C.sub.3-C.sub.10cycloalkyl,
C.sub.3-C.sub.10cycloalkyl-C.sub.1-C.sub.10alkyl-,
C.sub.1-C.sub.10haloalkyl, C.sub.2-C.sub.10alkenyl,
C.sub.2-C.sub.10alkynyl,
C.sub.1-C.sub.4alkoxy-C.sub.1-C.sub.10alkyl-,
C.sub.1-C.sub.4alkylthio-C.sub.1-C.sub.4alkyl-,
C.sub.1-C.sub.10alkoxy, C.sub.2-C.sub.10alkenyloxy,
C.sub.2-C.sub.10alkynyloxy, C.sub.1-C.sub.10alkylthio-,
N--C.sub.1-C.sub.4alkyl-amino-, C.sub.4alkyl)-amino-, aryl or aryl
substituted by one to three R.sup.14, which may be the same or
different, heteroaryl or heteroaryl substituted by one to three
R.sup.14, which may be the same or different,
aryl-C.sub.1-C.sub.4alkyl- or aryl-C.sub.1-C.sub.4alkyl- wherein
the aryl moiety is substituted by one to three R.sup.14, which may
be the same or different, heteroaryl-C.sub.1-C.sub.4alkyl- or
heteroaryl-C.sub.1-C.sub.4alkyl- wherein the heteroaryl moiety is
substituted by one to three R.sup.14, which may be the same or
different, aryloxy- or aryloxy-substituted by one to three
R.sup.14, which may be the same or different, heteroaryloxy- or
heteroaryloxy-substituted by one to three R.sup.14, which may be
the same or different, arylthio- or arylthio-substituted by one to
three R.sup.14, which may be the same or different, or
heteroarylthio- or heteroarylthio-substituted by one to three
R.sup.14, which may be the same or different; and each R.sup.14 is
independently halo, cyano, nitro, C.sub.1-C.sub.10alkyl,
C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.10alkoxy,
C.sub.1-C.sub.4alkoxycarbonyl-, C.sub.1-C.sub.4haloalkoxy,
C.sub.1-C.sub.10alkylthio-, C.sub.1-C.sub.4haloalkylthio-,
C.sub.1-C.sub.10alkylsulfinyl-, C.sub.1-C.sub.4haloalkylsulfinyl-,
C.sub.1-C.sub.10alkylsulfonyl-, C.sub.1-C.sub.4haloalkylsulfonyl-,
aryl or aryl substituted by one to five substituents independently
selected from halo, cyano, nitro, C.sub.1-C.sub.6alkyl,
C.sub.1-C.sub.6haloalkyl or C.sub.1-C.sub.6alkoxy, or heteroaryl or
heteroaryl substituted by one to four substituents independently
selected from halo, cyano, nitro, C.sub.1-C.sub.6alkyl,
C.sub.1-C.sub.6haloalkyl or C.sub.1-C.sub.6alkoxy. Such R.sup.5
groups may be metabolized, preferably in planta, to give the
corresponding compound wherein R.sup.5 is hydroxy.
[0048] In one preferred embodiment R.sup.5 is
iso-propylcarbonyloxy- or tert-butyl-carbonyloxy-.
[0049] Preferably each R.sup.6 is independently halo,
C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl,
C.sub.1-C.sub.4alkoxy or C.sub.1-C.sub.4haloalkoxy. Examples of
such preferred groups for R.sup.6 are chloro, fluoro, methyl,
ethyl, trifluoromethyl, methoxy or trifluoromethoxy.
[0050] Preferably each R.sup.7 is independently halo,
C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.r
C.sub.4alkoxy or C.sub.1-C.sub.4haloalkoxy. Examples of such
preferred groups for R.sup.7 are chloro, fluoro, methyl, ethyl,
trifluoromethyl, methoxy and trifluoromethoxy.
[0051] Preferably each R.sup.8 is independently halo, cyano, nitro,
C.sub.1-C.sub.10alkyl, C.sub.1-C.sub.4haloalkyl,
C.sub.1-C.sub.10alkoxy, C.sub.1-C.sub.4alkoxycarbonyl-,
C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.10alkylthio-,
C.sub.1-C.sub.4haloalkylthio-, C.sub.1-C.sub.10alkylsulfinyl-,
C.sub.1-C.sub.4haloalkylsulfinyl-, C.sub.1-C.sub.10alkylsulfonyl-
or C.sub.1-C.sub.4haloalkylsulfonyl-.
[0052] More preferably each R.sup.8 is independently halo, cyano,
nitro, C.sub.1-C.sub.10alkyl, C.sub.1-C.sub.4haloalkyl,
C.sub.1-C.sub.10alkoxy, C.sub.1-C.sub.4haloalkoxy,
C.sub.1-C.sub.10alkylthio or C.sub.1-C.sub.4haloalkylthio. Examples
of such more preferred groups for R.sup.8 are iodo, bromo, chloro,
fluoro, cyano, nitro, methyl, ethyl, trifluoromethyl, methoxy,
trifluoromethoxy and trifluoromethylthio.
[0053] Most preferably each R.sup.8 is independently halo,
C.sub.1-C.sub.10alkyl, C.sub.1-C.sub.4haloalkyl,
C.sub.1-C.sub.10alkoxy or C.sub.1-C.sub.4haloalkoxy. Examples of
such most preferred groups for R.sup.8 are bromo, chloro, fluoro,
methyl, ethyl, trifluoromethyl, methoxy and trifluoromethoxy.
[0054] Preferably R.sup.9 is C.sub.2-C.sub.10alkenyl,
C.sub.2-C.sub.10alkynyl, RO.sub.2C--C.sub.1-C.sub.4alkyl- or
RO.sub.2C--C.sub.1-C.sub.4alkyl- wherein R is C.sub.1-C.sub.4alkyl,
or aryl-C.sub.1-C.sub.4alkyl- or aryl-C.sub.1-C.sub.4alkyl- wherein
the aryl moiety is substituted by one to three R.sup.13, which may
be the same or different, more preferably R.sup.9 is
C.sub.3-C.sub.4alkenyl, C.sub.3-C.sub.4alkynyl, RO.sub.2C-methyl-
or RO.sub.2C-methyl- wherein R is C.sub.1-C.sub.4alkyl, or benzyl
or benzyl wherein the phenyl moiety is substituted by one to three
R.sup.13, which may be the same or different, even more preferably
R.sup.9 is allyl, propargyl or benzyl, most preferably R.sup.9 is
allyl.
[0055] Preferably R.sup.10 is C.sub.1-C.sub.4alkyl,
C.sub.3-C.sub.6cycloalkyl,
C.sub.3-C.sub.10cycloalkyl-C.sub.1-C.sub.10alkyl,
C.sub.1-C.sub.4haloalkyl, C.sub.2-C.sub.4alkenyl,
C.sub.2-C.sub.4alkynyl, C.sub.1-C.sub.4alkoxy-C.sub.1-C.sub.4alkyl,
C.sub.1-C.sub.4alkylthio-C.sub.1-C.sub.4alkyl,
C.sub.1-C.sub.4alkoxy, C.sub.2-C.sub.4alkenyloxy,
C.sub.2-C.sub.4alkynyloxy, C.sub.1-C.sub.4alkylthio,
N--C.sub.1-C.sub.4alkyl-amino, N,N-di-(C.sub.1-C.sub.4alkyl)-amino,
aryl or aryl substituted by one to three R.sup.14, which may be the
same or different, heteroaryl or heteroaryl substituted by one to
three R.sup.14, which may be the same or different,
aryl-C.sub.1-C.sub.4alkyl or aryl-C.sub.1-C.sub.4alkyl wherein the
aryl moiety is substituted by one to three R.sup.14, which may be
the same or different, heteroaryl-C.sub.1-C.sub.4alkyl or
heteroaryl-C.sub.1-C.sub.4alkyl wherein the heteroaryl moiety is
substituted by one to three R.sup.14, which may be the same or
different, aryloxy or aryloxy substituted by one to three R.sup.14,
which may be the same or different, heteroaryloxy or heteroaryloxy
substituted by one to three R.sup.14, which may be the same or
different, arylthio or arylthio substituted by one to three
R.sup.14, which may be the same or different, heteroarylthio or
heteroarylthio substituted by one to three R.sup.14, which may be
the same or different, or RO.sub.2C-carbonyl- or
RO.sub.2C-carbonyl- wherein R is C.sub.1-C.sub.4alkyl.
[0056] More preferably R.sup.10 is iso-propyl, tert-butyl,
cyclopropyl, ethoxy, methylthio, ethylthio, or phenylthio.
[0057] Most preferably R.sup.10 is iso-propyl or tert-butyl.
[0058] Preferably each R.sup.11 is independently
C.sub.1-C.sub.4alkyl.
[0059] Preferably R.sup.12 is C.sub.1-C.sub.4alkyl or
C.sub.1-C.sub.4haloalkyl, most preferably methyl or
trifluoromethyl.
[0060] Preferably each R.sup.13 is independently halo, nitro,
C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl or
C.sub.1-C.sub.4alkoxy. Examples of such preferred groups are
chloro, fluoro, nitro, methyl, ethyl, trifluoromethyl and
methoxy.
[0061] Preferably each R.sup.14 is independently halo, nitro,
C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl,
C.sub.1-C.sub.4alkoxy or C.sub.1-C.sub.4haloalkoxy. Examples of
such preferred groups are chloro, fluoro, nitro, methyl, ethyl,
trifluoromethyl, methoxy and trifluoromethoxy.
[0062] In one embodiment the invention provides a compound of
formula (X)
##STR00007##
wherein R.sup.1, R.sup.2, R.sup.4 and R.sup.5 are as defined for a
compound of formula (I) and R.sup.3 is C.sub.1-C.sub.10alkyl,
C.sub.2-C.sub.10alkenyl, C.sub.2-C.sub.10alkynyl,
C.sub.3-C.sub.10cycloalkyl,
C.sub.3-C.sub.10cycloalkyl-C.sub.1-C.sub.6alkyl-,
C.sub.1-C.sub.10alkoxy-C.sub.1-C.sub.6alkyl-,
C.sub.1-C.sub.10cyanoalkyl-,
C.sub.1-C.sub.10alkoxycarbonyl-C.sub.1-C.sub.6alkyl-,
N--C.sub.1-C.sub.3alkyl-aminocarbonyl-C.sub.1-C.sub.6alkyl-,
N,N-di-(C.sub.1-C.sub.3alkyl)-aminocarbonyl-C.sub.1-C.sub.6alkyl-,
aryl-C.sub.1-C.sub.6alkyl- or aryl-C.sub.1-C.sub.6alkyl- wherein
the aryl moiety is substituted by one to three R.sup.7, which may
be the same or different, or heterocyclyl-C.sub.1-C.sub.6alkyl- or
heterocyclyl-C.sub.1-C.sub.6alkyl- wherein the heterocyclyl moiety
is substituted by one to three R.sup.7, which may be the same or
different; or a salt or N-oxide thereof. The preferences for
R.sup.1, R.sup.2, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8,
R.sup.9, R.sup.10, R.sup.11, R.sup.12, R.sup.13 and R.sup.14 are
the same as the preferences set out for the corresponding
substituents of a compound of formula (I). The preferences for
R.sup.3 are the same as the preferences set out for the
corresponding substituents of a compound of formula (I) except that
R.sup.3 cannot be hydrogen.
[0063] In another embodiment the invention provides a compound of
formula (C)
##STR00008##
wherein R.sup.1, R.sup.2 and R.sup.4 are as defined for a compound
of formula (I) and R.sup.3 is C.sub.1-C.sub.10alkyl,
C.sub.2-C.sub.10alkenyl, C.sub.2-C.sub.10alkynyl,
C.sub.3-C.sub.10cycloalkyl,
C.sub.3-C.sub.10cycloalkyl-C.sub.1-C.sub.6alkyl-,
C.sub.1-C.sub.10alkoxy-C.sub.1-C.sub.6alkyl-,
C.sub.1-C.sub.10cyanoalkyl-,
C.sub.1-C.sub.10alkoxycarbonyl-C.sub.1-C.sub.6alkyl-,
N--C.sub.1-C.sub.3alkyl-aminocarbonyl-C.sub.1-C.sub.6alkyl-,
N,N-di-(C.sub.1-C.sub.3alkyl)-aminocarbonyl-C.sub.1-C.sub.6alkyl-,
aryl-C.sub.1-C.sub.6alkyl- or aryl-C.sub.1-C.sub.6alkyl- wherein
the aryl moiety is substituted by one to three R.sup.7, which may
be the same or different, or heterocyclyl-C.sub.1-C.sub.6alkyl- or
heterocyclyl-C.sub.1-C.sub.6alkyl- wherein the heterocyclyl moiety
is substituted by one to three R.sup.7, which may be the same or
different; and R.sup.5 is R.sup.9-oxy-, R.sup.10-carbonyloxy-,
tri-R.sup.11-silyloxy- or R.sup.12-sulfonyloxy-; or a salt or
N-oxide thereof. The preferences for R.sup.1, R.sup.2, R.sup.4,
R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.11, R.sup.12,
R.sup.13 and R.sup.14 are the same as the preferences set out for
the corresponding substituents of a compound of formula (I). The
preferences for R.sup.3 are the same as the preferences set out for
the corresponding substituents of a compound of formula (I) except
that R.sup.3 cannot be hydrogen. The preferences for R.sup.5 are
the same as the preferences set out for the corresponding
substituents of a compound of formula (I) except that R.sup.5
cannot be hydroxy.
[0064] In another embodiment the invention provides a compound of
formula (D)
##STR00009##
wherein R.sup.1, R.sup.2 and R.sup.4 are as defined for a compound
of formula (I) and R.sup.3 is C.sub.1-C.sub.10alkyl,
C.sub.2-C.sub.10alkenyl, C.sub.2-C.sub.10alkynyl,
C.sub.3-C.sub.10cycloalkyl,
C.sub.3-C.sub.10cycloalkyl-C.sub.1-C.sub.6alkyl-,
C.sub.1-C.sub.10alkoxy-C.sub.1-C.sub.6alkyl-,
C.sub.1-C.sub.10cyanoalkyl-,
C.sub.1-C.sub.10alkoxycarbonyl-C.sub.1-C.sub.6alkyl-,
N--C.sub.1-C.sub.3alkyl-aminocarbonyl-C.sub.1-C.sub.6alkyl-,
N,N-di-(C.sub.1-C.sub.3alkyl)-aminocarbonyl-C.sub.1-C.sub.6alkyl-,
aryl-C.sub.1-C.sub.6alkyl- or aryl-C.sub.1-C.sub.6alkyl- wherein
the aryl moiety is substituted by one to three R.sup.7, which may
be the same or different, or heterocyclyl-C.sub.1-C.sub.6alkyl- or
heterocyclyl-C.sub.1-C.sub.6alkyl- wherein the heterocyclyl moiety
is substituted by one to three R.sup.7, which may be the same or
different; or a salt or N-oxide thereof. The preferences for
R.sup.1, R.sup.2, R.sup.4, R.sup.6, R.sup.7, R.sup.8 and R.sup.13
are the same as the preferences set out for the corresponding
substituents of a compound of formula (I). The preferences for
R.sup.3 are the same as the preferences set out for the
corresponding substituents of a compound of formula (I) except that
R.sup.3 cannot be hydrogen.
[0065] Certain intermediates are novel and as such form part of the
invention. One such group are compounds of formula (J) wherein
R.sup.1, R.sup.2, and R.sup.4 are as defined for a compound of
formula (I); and R.sup.16 is C.sub.1-C.sub.6alkyl; or a salt or
N-oxide thereof.
##STR00010##
The preferences for R.sup.1, R.sup.2, and R.sup.4 are the same as
the preferences set out for the corresponding substituents of a
compound of formula (I). Preferably R.sup.16 is methyl or ethyl,
most preferably methyl.
[0066] Another group are compounds of formula (K) wherein R.sup.1,
R.sup.2, and R.sup.4 are as defined for a compound of formula (I);
R.sup.3 is C.sub.1-C.sub.10alkyl, C.sub.2-C.sub.10alkenyl,
C.sub.2-C.sub.10alkynyl, C.sub.3-C.sub.10cycloalkyl,
C.sub.3-C.sub.10cycloalkyl-C.sub.1-C.sub.6alkyl-,
C.sub.1-C.sub.10alkoxy-C.sub.1-C.sub.6alkyl-,
C.sub.1-C.sub.10cyanoalkyl-,
C.sub.1-C.sub.10alkoxycarbonyl-C.sub.1-C.sub.6alkyl-,
N--C.sub.1-C.sub.3alkyl-aminocarbonyl-C.sub.1-C.sub.6alkyl-,
N,N-di-(C.sub.1-C.sub.3alkyl)-aminocarbonyl-C.sub.1-C.sub.6alkyl-,
aryl-C.sub.1-C.sub.6alkyl- or aryl-C.sub.1-C.sub.6alkyl- wherein
the aryl moiety is substituted by one to three R.sup.7, which may
be the same or different, or heterocyclyl-C.sub.1-C.sub.6alkyl- or
heterocyclyl-C.sub.1-C.sub.6alkyl- wherein the heterocyclyl moiety
is substituted by one to three R.sup.7, which may be the same or
different; and R.sup.16 is C.sub.1-C.sub.6alkyl; or a salt or
N-oxide thereof.
##STR00011##
The preferences for R.sup.1, R.sup.2, and R.sup.4 are the same as
the preferences set out for the corresponding substituents of a
compound of formula (I). The preferences for R.sup.3 are the same
as the preferences set out for the corresponding substituents of a
compound of formula (I) except that R.sup.3 cannot be hydrogen.
Preferably R.sup.16 is methyl or ethyl, most preferably methyl.
[0067] The compounds in Tables 1 to 29 below illustrate the
compounds of the invention.
TABLE-US-00001 TABLE 1 Table 1 provides 70 compounds of formula
(I), where R.sup.1 and R.sup.2 are both hydrogen, R.sup.4 is
2,5-bis-(trifluoromethyl)-phenyl, and R.sup.3 and R.sup.5 have the
values listed in Table 1. (I) ##STR00012## Compound number R.sup.3
R.sup.5 1.001 H --OH 1.002 H --OCOCH.sub.3 1.003 H
--OCOCH.sub.2CH.sub.3 1.004 H --OCOCH(CH.sub.3).sub.2 1.005 H
--OCO(CH.sub.2).sub.2CH.sub.3 1.006 H
--OCOCH(CH.sub.3)CH.sub.2CH.sub.3 1.007 H
--OCOCH.sub.2CH(CH.sub.3).sub.2 1.008 H --OCOC(CH.sub.3).sub.3
1.009 H --O(CO)OCH.sub.2CH.sub.3 1.010 H --O(CO)SCH.sub.2CH.sub.3
1.011 --CH.sub.3 --OH 1.012 --CH.sub.3 --OCOCH.sub.3 1.013
--CH.sub.3 --OCOCH.sub.2CH.sub.3 1.014 --CH.sub.3
--OCOCH(CH.sub.3).sub.2 1.015 --CH.sub.3
--OCO(CH.sub.2).sub.2CH.sub.3 1.016 --CH.sub.3
--OCOCH(CH.sub.3)CH.sub.2CH.sub.3 1.017 --CH.sub.3
--OCOCH.sub.2CH(CH.sub.3).sub.2 1.018 --CH.sub.3
--OCOC(CH.sub.3).sub.3 1.019 --CH.sub.3 --O(CO)OCH.sub.2CH.sub.3
1.020 --CH.sub.3 --O(CO)SCH.sub.2CH.sub.3 1.021 --CH.sub.2CH.sub.3
--OH 1.022 --CH.sub.2CH.sub.3 --OCOCH.sub.3 1.023
--CH.sub.2CH.sub.3 --OCOCH.sub.2CH.sub.3 1.024 --CH.sub.2CH.sub.3
--OCOCH(CH.sub.3).sub.2 1.025 --CH.sub.2CH.sub.3
--OCO(CH.sub.2).sub.2CH.sub.3 1.026 --CH.sub.2CH.sub.3
--OCOCH(CH.sub.3)CH.sub.2CH.sub.3 1.027 --CH.sub.2CH.sub.3
--OCOCH.sub.2CH(CH.sub.3).sub.2 1.028 --CH.sub.2CH.sub.3
--OCOC(CH.sub.3).sub.3 1.029 --CH.sub.2CH.sub.3
--O(CO)OCH.sub.2CH.sub.3 1.030 --CH.sub.2CH.sub.3
--O(CO)SCH.sub.2CH.sub.3 1.031 --CH.sub.2CHF.sub.2 --OH 1.032
--CH.sub.2CHF.sub.2 --OCOCH.sub.3 1.033 --CH.sub.2CHF.sub.2
--OCOCH.sub.2CH.sub.3 1.034 --CH.sub.2CHF.sub.2
--OCOCH(CH.sub.3).sub.2 1.035 --CH.sub.2CHF.sub.2
--OCO(CH.sub.2).sub.2CH.sub.3 1.036 --CH.sub.2CHF.sub.2
--OCOCH(CH.sub.3)CH.sub.2CH.sub.3 1.037 --CH.sub.2CHF.sub.2
--OCOCH.sub.2CH(CH.sub.3).sub.2 1.038 --CH.sub.2CHF.sub.2
--OCOC(CH.sub.3).sub.3 1.039 --CH.sub.2CHF.sub.2
--O(CO)OCH.sub.2CH.sub.3 1.040 --CH.sub.2CHF.sub.2
--O(CO)SCH.sub.2CH.sub.3 1.041 --CH.sub.2CF.sub.3 --OH 1.042
--CH.sub.2CF.sub.3 --OCOCH.sub.3 1.043 --CH.sub.2CF.sub.3
--OCOCH.sub.2CH.sub.3 1.044 --CH.sub.2CF.sub.3
--OCOCH(CH.sub.3).sub.2 1.045 --CH.sub.2CF.sub.3
--OCO(CH.sub.2).sub.2CH.sub.3 1.046 --CH.sub.2CF.sub.3
--OCOCH(CH.sub.3)CH.sub.2CH.sub.3 1.047 --CH.sub.2CF.sub.3
--OCOCH.sub.2CH(CH.sub.3).sub.2 1.048 --CH.sub.2CF.sub.3
--OCOC(CH.sub.3).sub.3 1.049 --CH.sub.2CF.sub.3
--O(CO)OCH.sub.2CH.sub.3 1.050 --CH.sub.2CF.sub.3
--O(CO)SCH.sub.2CH.sub.3 1.051 --CH.sub.2CH.dbd.CH.sub.2 --OH 1.052
--CH.sub.2CH.dbd.CH.sub.2 --OCOCH.sub.3 1.053
--CH.sub.2CH.dbd.CH.sub.2 --OCOCH.sub.2CH.sub.3 1.054
--CH.sub.2CH.dbd.CH.sub.2 --OCOCH(CH.sub.3).sub.2 1.055
--CH.sub.2CH.dbd.CH.sub.2 --OCO(CH.sub.2).sub.2CH.sub.3 1.056
--CH.sub.2CH.dbd.CH.sub.2 --OCOCH(CH.sub.3)CH.sub.2CH.sub.3 1.057
--CH.sub.2CH.dbd.CH.sub.2 --OCOCH.sub.2CH(CH.sub.3).sub.2 1.058
--CH.sub.2CH.dbd.CH.sub.2 --OCOC(CH.sub.3).sub.3 1.059
--CH.sub.2CH.dbd.CH.sub.2 --O(CO)OCH.sub.2CH.sub.3 1.060
--CH.sub.2CH.dbd.CH.sub.2 --O(CO)SCH.sub.2CH.sub.3 1.061
--CH.sub.2C.ident.CH --OH 1.062 --CH.sub.2C.ident.CH --OCOCH.sub.3
1.063 --CH.sub.2C.ident.CH --OCOCH.sub.2CH.sub.3 1.064
--CH.sub.2C.ident.CH --OCOCH(CH.sub.3).sub.2 1.065
--CH.sub.2C.ident.CH --OCO(CH.sub.2).sub.2CH.sub.3 1.066
--CH.sub.2C.ident.CH --OCOCH(CH.sub.3)CH.sub.2CH.sub.3 1.067
--CH.sub.2C.ident.CH --OCOCH(CH.sub.3).sub.2 1.068
--CH.sub.2C.ident.CH --OCOC(CH.sub.3).sub.3 1.069
--CH.sub.2C.ident.CH --O(CO)OCH.sub.2CH.sub.3 1.070
--CH.sub.2C.ident.CH --O(CO)SCH.sub.2CH.sub.3
Table 2:
[0068] Table 2 provides 70 compounds of formula (I), where R.sup.1
and R.sup.2 are both hydrogen, R.sup.4 is
3-bromo-2-chloro-6-fluoro-phenyl, and R.sup.3 and R.sup.5 have the
values listed in Table 1.
Table 3:
[0069] Table 3 provides 70 compounds of formula (I), where R.sup.1
and R.sup.2 are both hydrogen, R.sup.4 is
4-bromo-2-trifluoromethyl-phenyl, and R.sup.3 and R.sup.5 have the
values listed in Table 1.
Table 4:
[0070] Table 4 provides 70 compounds of formula (I), where R.sup.1
and R.sup.2 are both hydrogen, R.sup.4 is
2-chloro-3,6-difluoro-phenyl, and R.sup.3 and R.sup.5 have the
values listed in Table 1.
Table 5:
[0071] Table 5 provides 70 compounds of formula (I), where R.sup.1
and R.sup.2 are both hydrogen, R.sup.4 is 2-chloro-4-fluoro-phenyl,
and R.sup.3 and R.sup.5 have the values listed in Table 1.
Table 6:
[0072] Table 6 provides 70 compounds of formula (I), where R.sup.1
and R.sup.2 are both hydrogen, R.sup.4 is 2-chloro-5-fluoro-phenyl,
and R.sup.3 and R.sup.5 have the values listed in Table 1.
Table 7:
[0073] Table 7 provides 70 compounds of formula (I), where R.sup.1
and R.sup.2 are both hydrogen, R.sup.4 is 2-chloro-phenyl, and
R.sup.3 and R.sup.5 have the values listed in Table 1.
Table 8:
[0074] Table 8 provides 70 compounds of formula (I), where R.sup.1
and R.sup.2 are both hydrogen, R.sup.4 is,
2-chloro-3-trifluoromethyl-phenyl, and R.sup.3 and R.sup.5 have the
values listed in Table 1.
Table 9:
[0075] Table 9 provides 70 compounds of formula (I), where R.sup.1
and R.sup.2 are both hydrogen, R.sup.4 is
2-chloro-5-trifluoromethyl-phenyl, and R.sup.3 and R.sup.5 have the
values listed in Table 1.
Table 10:
[0076] Table 10 provides 70 compounds of formula (I), where R.sup.1
and R.sup.2 are both hydrogen, R.sup.4 is
2-chloro-6-trifluoromethyl-phenyl, and R.sup.3 and R.sup.5 have the
values listed in Table 1.
Table 11:
[0077] Table 11 provides 70 compounds of formula (I), where R.sup.1
and R.sup.2 are both hydrogen, R.sup.4 is
4-chloro-2-trifluoromethyl-phenyl, and R.sup.3 and R.sup.5 have the
values listed in Table 1.
Table 12:
[0078] Table 12 provides 70 compounds of formula (I), where R.sup.1
and R.sup.2 are both hydrogen, R.sup.4 is
5-chloro-2-trifluoromethyl-phenyl, and R.sup.3 and R.sup.5 have the
values listed in Table 1.
Table 13:
[0079] Table 13 provides 70 compounds of formula (I), where R.sup.1
and R.sup.2 are both hydrogen, R.sup.4 is
2,3-dichloro-6-fluoro-phenyl, and R.sup.3 and R.sup.5 have the
values listed in Table 1.
Table 14:
[0080] Table 14 provides 70 compounds of formula (I), where R.sup.1
and R.sup.2 are both hydrogen, R.sup.4 is
2,4-dichloro-5-fluoro-phenyl, and R.sup.3 and R.sup.5 have the
values listed in Table 1.
Table 15:
[0081] Table 15 provides 70 compounds of formula (I), where R.sup.1
and R.sup.2 are both hydrogen, R.sup.4 is
3,5-dichloro-2-methoxy-phenyl, and R.sup.3 and R.sup.5 have the
values listed in Table 1.
Table 16:
[0082] Table 16 provides 70 compounds of formula (I), where R.sup.1
and R.sup.2 are both hydrogen, R.sup.4 is 2,3-dichloro-phenyl, and
R.sup.3 and R.sup.5 have the values listed in Table 1.
Table 17:
[0083] Table 17 provides 70 compounds of formula (I), where R.sup.1
and R.sup.2 are both hydrogen, R.sup.4 is 2,4-dichloro-phenyl, and
R.sup.3 and R.sup.5 have the values listed in Table 1.
Table 18:
[0084] Table 18 provides 70 compounds of formula (I), where R.sup.1
and R.sup.2 are both hydrogen, R.sup.4 is 2,5-dichloro-phenyl, and
R.sup.3 and R.sup.5 have the values listed in Table 1.
Table 19:
[0085] Table 19 provides 70 compounds of formula (I), where R.sup.1
and R.sup.2 are both hydrogen, R.sup.4 is 2,6-dichloro-phenyl, and
R.sup.3 and R.sup.5 have the values listed in Table 1.
Table 20:
[0086] Table 20 provides 70 compounds of formula (I), where R.sup.1
and R.sup.2 are both hydrogen, R.sup.4 is
2,6-dichloro-4-trifluoromethoxy-phenyl, and R.sup.3 and R.sup.5
have the values listed in Table 1.
Table 21:
[0087] Table 21 provides 70 compounds of formula (I), where R.sup.1
and R.sup.2 are both hydrogen, R.sup.4 is
2,6-dichloro-4-trifluoromethyl-phenyl, and R.sup.3 and R.sup.5 have
the values listed in Table 1.
Table 22:
[0088] Table 22 provides 70 compounds of formula (I), where R.sup.1
and R.sup.2 are both hydrogen, R.sup.4 is
2,6-diethyl-4-methyl-phenyl, and R.sup.3 and R.sup.5 have the
values listed in Table 1.
Table 23:
[0089] Table 23 provides 70 compounds of formula (I), where R.sup.1
and R.sup.2 are both hydrogen, R.sup.4 is 2,3-dimethoxy-phenyl, and
R.sup.3 and R.sup.5 have the values listed in Table 1.
Table 24:
[0090] Table 24 provides 70 compounds of formula (I), where R.sup.1
and R.sup.2 are both hydrogen, R.sup.4 is 2-iodo-phenyl, and
R.sup.3 and R.sup.5 have the values listed in Table 1.
Table 25:
[0091] Table 25 provides 70 compounds of formula (I), where R.sup.1
and R.sup.2 are both hydrogen, R.sup.4 is
2-methoxy-5-trifluoromethoxy-phenyl, and R.sup.3 and R.sup.5 have
the values listed in Table 1.
Table 26:
[0092] Table 26 provides 70 compounds of formula (I), where R.sup.1
and R.sup.2 are both hydrogen, R.sup.4 is 2,3,6-trichloro-phenyl,
and R.sup.3 and R.sup.5 have the values listed in Table 1.
Table 27:
[0093] Table 27 provides 70 compounds of formula (I), where R.sup.1
and R.sup.2 are both hydrogen, R.sup.4 is
2-trifluoromethoxy-phenyl, and R.sup.3 and R.sup.5 have the values
listed in Table 1.
Table 28:
[0094] Table 28 provides 70 compounds of formula (I), where R.sup.1
and R.sup.2 are both hydrogen, R.sup.4 is 2-trifluoromethyl-phenyl,
and R.sup.3 and R.sup.5 have the values listed in Table 1.
Table 29:
[0095] Table 29 provides 70 compounds of formula (I), where R.sup.1
and R.sup.2 are both hydrogen, R.sup.4 is 2,4,6-trimethyl-phenyl,
and R.sup.3 and R.sup.5 have the values listed in Table 1.
[0096] The compounds of the invention may be made by a variety of
methods, for example, by the methods described in Schemes 1 to
10.
##STR00013##
[0097] 1) Compounds of formula (F) wherein R.sup.4 is as defined
for a compound of formula (I) can be prepared by reaction of a
benzyl halide of formula (E) wherein R.sup.4 is as defined for a
compound of formula (I) and X is halogen, such as bromine, with a
metal sulfite, such as sodium sulfite, as shown in Scheme 1. For
example, if (E) is a benzyl bromide (i.e. where X is bromine) the
reaction can conveniently be carried out in a suitable solvent,
such as water, optionally in the presence of a suitable co-solvent,
such as acetone, optionally using microwave heating. Similar
methods have been described, for example, in Synthetic
Communications 25(9), 1303, 1995. Compounds of formula (E) are
commercially available or can be made by methods known to the
person skilled in the art. A route to certain benzyl halides is,
for example, described in Scheme 6 below.
[0098] 2) Compounds of formula (G) wherein R.sup.4 is as defined
for a compound of formula (I) and X is halogen, such as chlorine,
can be prepared by treating a compound of formula (F) as defined in
1) with a halogenating agent, such as phosphorus pentachloride,
optionally in a suitable solvent, such as toluene, optionally using
microwave heating.
##STR00014##
[0099] 3) Compounds of formula (J) wherein R.sup.1, R.sup.2 and
R.sup.4 are as defined for a compound of formula (I) and R.sup.16
is C.sub.1-C.sub.6alkyl can be prepared by reaction of an
amino-pyrazine ester of formula (H) wherein R.sup.1 and R.sup.2 are
as defined for a compound of formula (I) and R.sup.16 is
C.sub.1-C.sub.6alkyl with an acid derivative of formula (G) as
defined in 2) as shown in Scheme 2. For example, if (G) is a
sulfonyl chloride (i.e. where X is chlorine) the reaction can
conveniently be carried out in the presence of a base, such as
triethylamine or pyridine, in a suitable solvent, such as
acetonitrile or dichloromethane, optionally using microwave
heating. Compounds of formula (H) are commercially available or can
be made by methods known to the person skilled in the art.
[0100] 4) Compounds of formula (K), wherein R.sup.1, R.sup.2,
R.sup.3 and R.sup.4 are as defined for a compound of formula (I)
and R.sup.16 is C.sub.1-C.sub.6alkyl can be prepared from a
compound of formula (J) as defined in 3) by reaction with a
compound of formula R.sup.3LG wherein R.sup.3 is as defined for a
compound of formula (I) other than hydrogen, and LG is a leaving
group such as a halide, for example bromide or iodide, or tosylate,
mesylate or triflate, with a base, such as
N,N-diisopropylethylamine, in a suitable solvent, such as
acetonitrile, optionally using microwave heating.
[0101] 5) Compounds of formula (D), i.e. a compound of formula (I)
wherein R.sup.3 is as defined for a compound of formula (I) other
than hydrogen and R.sup.5 is hydroxy, can be prepared by treating a
compound of formula (K) as defined in 4) with a base, such as
lithium hexamethyldisilazide, sodium hexamethyldisilazide or
potassium carbonate, in a suitable solvent, such as tetrahydrofuran
or N,N-dimethylformamide, optionally using microwave heating.
[0102] 6) Compounds of formula (L), i.e. a compound of formula (I)
wherein R.sup.3 is as defined for a compound of formula (I) other
than hydrogen and R.sup.5 is --O--CO--R.sup.10, can be prepared by
reaction of a compound of formula (D) as defined in 5) with an acid
chloride of formula R.sup.10COCl or an acid anhydride of formula
(R.sup.10CO).sub.2O wherein R.sup.10 is as defined for a compound
of formula (I), optionally in the presence of a base, such as
pyridine or 4-dimethylaminopyridine, optionally in a suitable
solvent, such as dichloro-methane or acetonitrile, optionally using
microwave heating.
##STR00015##
[0103] 7) Compounds of formula (A), i.e. a compound of formula (I)
wherein R.sup.3 is hydrogen and R.sup.5 is hydroxy, can be prepared
by treating a compound of formula (J) as defined in 3) with a base,
such as lithium hexamethyldisilazide, sodium hexamethyl-disilazide
or potassium carbonate, in a suitable solvent, such as
tetrahydrofuran or N,N-dimethylformamide, optionally using
microwave heating, as shown in Scheme 3.
[0104] 8) Compounds of formula (M), i.e. a compound of formula (I)
wherein R.sup.3 is hydrogen and R.sup.5 is --O--CO--R.sup.10, can
be prepared by reaction of a compound of formula (A) as defined in
7) with an acid chloride of formula R.sup.10COCl or an acid
anhydride of formula (R.sup.10CO).sub.2O wherein R.sup.10 is as
defined for a compound of formula (I), optionally in the presence
of a base, such as pyridine, optionally in a suitable solvent, such
as dichloromethane, optionally using microwave heating.
##STR00016##
[0105] 9) Compounds of formula (L) as defined in 6), and compounds
of formula (N) wherein R.sup.1, R.sup.2, R.sup.4 and R.sup.10 are
as defined for a compound of formula (I) and R.sup.3 is as defined
for a compound of formula (I) other than hydrogen, can be prepared
from a compound of formula (M) as defined in 8) by reaction with a
compound of formula R.sup.3LG as defined in 4) in the presence of a
base, such as N,N-diisopropylethylamine, in a suitable solvent,
such as acetonitrile or N,N-dimethylformamide, optionally using
microwave heating, as shown in Scheme 4. The nature of the compound
of formula R.sup.3LG and the choice of base can determine the ratio
of compounds of formula (L) and compounds of formula (N).
[0106] 10) Compounds of formula (D) as defined in 5) can be
prepared by treating a compound of formula (L) as defined in 6)
with a base, such as sodium hydroxide or potassium
trimethylsilanolate, in a suitable solvent, such as tetrahydrofuran
or aqueous methanol.
[0107] 11) Compounds of formula (P), i.e. a compound of formula (I)
wherein R.sup.3 is as defined for a compound of formula (I) other
than hydrogen and R.sup.5 is --O--R.sup.9, can be prepared from a
compound of formula (D) as defined in 5) by reaction with a
compound of formula R.sup.9LG wherein R.sup.9 is as defined for a
compound of formula (I) and LG is a leaving group such as halide,
for example bromide or iodide, or tosylate, mesylate or triflate,
in the presence of a base, such as potassium carbonate, in a
suitable solvent, such as N,N-dimethylformamide or
acetonitrile.
##STR00017##
[0108] 12) Sulfonyl compounds of formula (R), i.e. a compound of
formula (I) wherein R.sup.3 is as defined for a compound of formula
(I) other than hydrogen and R.sup.5 is --O--SO.sub.2--R.sup.12, can
be prepared by reaction of a compound of formula (D) as defined in
5) with a sulfonyl chloride of formula R.sup.12SO.sub.2Cl or a
sulfonyl anhydride of formula (R.sup.12SO.sub.2).sub.2O wherein
R.sup.12 is as defined for a compound of formula (I), in the
presence of a base, such as N,N-diisopropylethylamine, optionally
in a suitable solvent, such as dichloromethane, optionally using
microwave heating, as shown in Scheme 5.
##STR00018##
[0109] 14) In certain cases where benzyl halides are not
commercially available it is necessary to make them. A typical
synthesis is shown in Scheme 6. Benzyl halides of formula (T)
wherein R.sup.8 is as defined for a compound of formula (I) and X
is halogen, such as bromine, can be made from a substituted toluene
of formula (S) wherein R.sup.8 is as defined for a compound of
formula (I), with a halogenating agent, such as halogen of formula
X.sub.2 wherein X is chlorine or bromine, in the presence of light,
or a N-halosuccinimide of formula
##STR00019##
wherein X is chlorine, bromine or iodine, in the presence of a
radical initiator, such as benzoyl peroxide, in a suitable solvent,
such as carbon tetrachloride, and optionally in the presence of a
light source, such as a 500 watt tungsten halogen lamp, at
reflux.
##STR00020##
[0110] 15) Compounds of formula (V) wherein R.sup.1, R.sup.2,
R.sup.5, and R.sup.8 are as defined for a compound of formula (I),
R.sup.3 is defined as for a compound of formula (I), n is 0 to 4,
and R.sup.17 is aryl or aryl substituted by one to three R.sup.13,
which may be the same or different, or heteroaryl or heteroaryl
substituted by one to three R.sup.13, which may be the same or
different, can be made from compounds of formula (U) wherein
R.sup.1, R.sup.2, R.sup.5, and R.sup.8 are as defined for a
compound of formula (I), R.sup.3 is defined as for a compound of
formula (I), n is 0 to 4, and Hal is chlorine, bromine or iodine,
using a Suzuki coupling with a boronic acid of the formula
R.sup.17B(OH).sub.2 or a Stille coupling with a tin compound of the
formula R.sup.17Sn(R.sup.18).sub.3 wherein R.sup.18 is
C.sub.1-C.sub.6alkyl as shown in Scheme 7. The Suzuki coupling is
typically carried out in the presence of a palladium catalyst, such
as palladium(II) acetate, in the presence of a ligand, such as
2'-dicyclohexylphosphino-2,6-dimethoxy-3-sulfonato-1,1'-biphenyl
hydrate sodium salt ("sodium S-Phos sulfonate"), in the presence of
a base, such as potassium phosphate, in a suitable solvent, such as
a mixture of toluene and water, at a temperature range from
50.degree. C. to 150.degree. C., preferably from 100.degree. C. to
120.degree. C., optionally using microwave heating. The Stille
coupling is typically carried out in the presence of a palladium
catalyst, such as palladium(II) chloride, in the presence of a
ligand, such as tri-tert-butylphosphine, in a suitable solvent,
such as N,N-dimethylformamide or acetonitrile, at temperature range
from 20.degree. C. to 150.degree. C., preferably from 75.degree. C.
to 120.degree. C.
##STR00021##
[0111] 16) Compounds of formula (2) wherein R.sup.3 and R.sup.4 are
as defined for a compound of formula (I) can be prepared by
reaction of an amine of formula (I) wherein R.sup.3 is as defined
for a compound of formula (I) with an acid derivative of formula
(G) as defined in 2) as shown in Scheme 8. For example, if (G) is a
sulfonyl chloride (i.e. where X is chlorine) the reaction can
conveniently be carried out in the presence of a base, such as
triethylamine or pyridine, in a suitable solvent, such as
acetonitrile or dichloromethane, optionally using microwave
heating. Amines of formula (I) are commercially available or can be
made by methods known to the person skilled in the art.
[0112] 17) Compounds of formula (D) as defined in 5) can be
prepared by reaction of a sulfonamide derivative of formula (2) as
defined in 1) with a chloropyrazine ester of formula (3) wherein
R.sup.1 and R.sup.2 are as defined for a compound of formula (I)
and R.sup.16 is as defined in 3). The reaction can conveniently be
carried out in the presence of a base, such as potassium carbonate,
in a suitable solvent, such as N,N-dimethylformamide, optionally
using microwave heating. Compounds of formula (3) can be made by
methods known to the person skilled in the art, particularly
following Molbank 2002, M287 (see http://www.mdpi.org/molbank).
##STR00022##
[0113] 18) Compounds of formula (5) wherein R.sup.1 and R.sup.2 are
as defined for a compound of formula (I) and R.sup.16 is as defined
in 3) can be made by reaction of an aminopyrazine ester of formula
(H) as defined in 3) with a sulfo-acetic ester of formula (4)
wherein R.sup.16 is as defined in 3), in the presence of a base,
such as pyridine, in a suitable solvent, such as dichloromethane,
as shown in Scheme 9. Sulfo-acetic esters of formula (4) can be
made by methods known to the person skilled in the art.
[0114] 19) Compounds of formula (6), wherein R.sup.1, R.sup.2 and
R.sup.3 are as defined for a compound of formula (I) and R.sup.16
is as defined in 3) can be prepared from a compound of formula (5)
as defined in 18) by reaction with a compound of formula R.sup.3LG
as defined in 4), in the presence of a base, such as
N,N-diisopropylethylamine, in a suitable solvent, such as
acetonitrile, optionally using microwave heating.
[0115] 20) Compounds of formula (7), wherein R.sup.1, R.sup.2 and
R.sup.3 are as defined for a compound of formula (I) and R.sup.16
is as defined in 3), can be prepared by treating a compound of
formula (6) as defined in 19) with a base, such as lithium
hexamethyl-disilazide, sodium hexamethyldisilazide or potassium
carbonate, in a suitable solvent, such as tetrahydrofuran or
N,N-dimethylformamide, optionally using microwave heating.
[0116] 21) Compounds of formula (8) wherein R.sup.1, R.sup.2 and
R.sup.3 are as defined for a compound of formula (I) can be made by
hydrolysis and decarboxylation of a compound of formula (7) as
defined in 20) by treatment with strong aqueous acid, such as
concentrated hydrochloric acid, or alternatively by treatment with
dilute aqueous acid, such as aqueous hydrochloric acid, in a
suitable solvent, such as ethanol, optionally using microwave
heating.
[0117] 22) Compounds of formula (10) wherein R.sup.1, R.sup.2,
R.sup.3, R.sup.8 and R.sup.10 are as defined for a compound of
formula (I) can be made by reaction of a compound of formula (8) as
defined in 21) with a lead compound of formula (9) wherein R.sup.8
is as defined for a compound of formula (I) and n is 0 to 5, in the
presence of a base, such as 4-dimethylaminopyridine, and in a
suitable solvent, such as chloroform or toluene, followed by
addition of an acid chloride of formula R.sup.10COCl or an acid
anhydride of formula (R.sup.10CO).sub.2O wherein R.sup.10 is as
defined for a compound of formula (I). Lead compounds of formula
(9) are known from the literature and can be made by the methods of
J. T. Pinhey, B. A. Rowe, Aust. J. Chem., 1979, 32, 1561-6; J.
Morgan, J. T. Pinhey, S. Chem. Soc. Perkin Trans. 1; 1990, 3,
715-20).
##STR00023##
[0118] 23) N-oxides of formula (D'), i.e. compounds of formula (D)
wherein the 5-nitrogen is oxidised, can be made by reaction of a
compound of formula (D) as defined in 5), with an oxidising agent,
for example a per-acid, such as trifluoroperacetic acid, generated
in situ for example by adding trifluoroacetic anhydride to urea
hydrogen peroxide, in a suitable solvent, such as dichloromethane,
as shown in Scheme 10.
[0119] The compounds of formula (I) according to the invention can
be used as herbicides in unmodified form, as obtained in the
synthesis, but they are generally formulated into herbicidal
compositions in various ways using formulation adjuvants, such as
carriers, solvents and surface-active substances. The formulations
can be in various physical forms, e.g. in the form of dusting
powders, gels, wettable powders, water-dispersible granules,
water-dispersible tablets, effervescent pellets, emulsifiable
concentrates, microemulsifiable concentrates, oil-in-water
emulsions, oil-flowables, aqueous dispersions, oily dispersions,
suspo-emulsions, capsule suspensions, emulsifiable granules,
soluble liquids, water-soluble concentrates (with water or a
water-miscible organic solvent as carrier), impregnated polymer
films or in other forms known e.g. from the Manual on Development
and Use of FAO Specifications for Plant Protection Products, 5th
Edition, 1999. Such formulations can either be used directly or
they are diluted prior to use. The dilutions can be made, for
example, with water, liquid fertilizers, micronutrients, biological
organisms, oil or solvents.
[0120] The formulations can be prepared e.g. by mixing the active
ingredient with the formulation adjuvants in order to obtain
compositions in the form of finely divided solids, granules,
solutions, dispersions or emulsions. The active ingredients can
also be, formulated with other adjuvants, such as finely divided
solids, mineral oils, oils of vegetable or animal origin, modified
oils of vegetable or animal origin, organic solvents, water,
surface-active substances or combinations thereof. The active
ingredients can also be contained in very fine microcapsules
consisting of a polymer. Microcapsules contain the active
ingredients in a porous carrier. This enables the active
ingredients to be released into the environment in controlled
amounts (e.g. slow-release). Microcapsules usually have a diameter
of from 0.1 to 500 microns. They contain active ingredients in an
amount of about from 25 to 95% by weight of the capsule weight. The
active ingredients can be in the form of a monolithic solid, in the
form of fine particles in solid or liquid dispersion or in the form
of a suitable solution. The encapsulating membranes comprise, for
example, natural or synthetic rubbers, cellulose, styrene/butadiene
copolymers, polyacrylonitrile, polyacrylate, polyesters,
polyamides, polyureas, polyurethane or chemically modified polymers
and starch xanthates or other polymers that are known to the person
skilled in the art in this connection. Alternatively, very fine
microcapsules can be formed in which the active ingredient is
contained in the form of finely divided particles in a solid matrix
of base substance, but the microcapsules are not themselves
encapsulated.
[0121] The formulation adjuvants that are suitable for the
preparation of the compositions according to the invention are
known per se. As liquid carriers there may be used: water, toluene,
xylene, petroleum ether, vegetable oils, acetone, methyl ethyl
ketone, cyclohexanone, acid anhydrides, acetonitrile, acetophenone,
amyl acetate, 2-butanone, butylene carbonate, chlorobenzene,
cyclohexane, cyclohexanol, alkyl esters of acetic acid, diacetone
alcohol, 1,2-dichloropropane, diethanolamine, p-diethylbenzene,
diethylene glycol, diethylene glycol abietate, diethylene glycol
butyl ether, diethylene glycol ethyl ether, diethylene glycol
methyl ether, N,N-dimethylformamide, dimethyl sulfoxide,
1,4-dioxane, dipropylene glycol, dipropylene glycol methyl ether,
dipropylene glycol dibenzoate, diproxitol, alkylpyrrolidone, ethyl
acetate, 2-ethylhexanol, ethylene carbonate, 1,1,1-trichloroethane,
2-heptanone, alpha-pinene, d-limonene, ethyl lactate, ethylene
glycol, ethylene glycol butyl ether, ethylene glycol methyl ether,
gamma-butyrolactone, glycerol, glycerol acetate, glycerol
diacetate, glycerol triacetate, hexadecane, hexylene glycol,
isoamyl acetate, isobornyl acetate, isooctane, isophorone,
isopropylbenzene, isopropyl myristate, lactic acid, laurylamine,
mesityl oxide, methoxy-propanol, methyl isoamyl ketone, methyl
isobutyl ketone, methyl laurate, methyl octanoate, methyl oleate,
methylene chloride, m-xylene, n-hexane, n-octylamine, octa-decanoic
acid, octylamine acetate, oleic acid, oleylamine, o-xylene, phenol,
polyethylene glycol (PEG400), propionic acid, propyl lactate,
propylene carbonate, propylene glycol, propylene glycol methyl
ether, p-xylene, toluene, triethyl phosphate, triethylene glycol,
xylenesulfonic acid, paraffin, mineral oil, trichloroethylene,
perchloroethylene, ethyl acetate, amyl acetate, butyl acetate,
propylene glycol methyl ether, diethylene glycol methyl ether,
methanol, ethanol, isopropanol, and alcohols of higher molecular
weight, such as amyl alcohol, tetrahydrofurfuryl alcohol, hexanol,
octanol, ethylene glycol, propylene glycol, glycerol,
N-methyl-2-pyrrolidone and the like. Water is generally the carrier
of choice for diluting the concentrates. Suitable solid carriers
are, for example, talc, titanium dioxide, pyrophyllite clay,
silica, attapulgite clay, kieselguhr, limestone, calcium carbonate,
bentonite, calcium montmorillonite, cottonseed husks, wheat flour,
soybean flour, pumice, wood flour, ground walnut shells, lignin and
similar substances, as described, for example, in CFR 180.1001. (c)
& (d).
[0122] A large number of surface-active substances can
advantageously be used in both solid and liquid formulations,
especially in those formulations which can be diluted with a
carrier prior to use. Surface-active substances may be anionic,
cationic, non-ionic or polymeric and they can be used as
emulsifiers, wetting agents or suspending agents or for other
purposes. Typical surface-active substances include, for example,
salts of alkyl sulfates, such as diethanolammonium lauryl sulfate;
salts of alkylarylsulfonates, such as calcium
dodecylbenzenesulfonate; alkylphenol/alkylene oxide addition
products, such as nonylphenol ethoxylate; alcohol/alkylene oxide
addition products, such as tridecylalcohol ethoxylate; soaps, such
as sodium stearate; salts of alkylnaphthalenesulfonates, such as
sodium dibutylnaphthalenesulfonate; dialkyl esters of
sulfosuccinate salts, such as sodium
di(2-ethylhexyl)sulfosuccinate; sorbitol esters, such as sorbitol
oleate; quaternary amines, such as lauryltrimethylammonium
chloride, polyethylene glycol esters of fatty acids, such as
polyethylene glycol stearate; block copolymers of ethylene oxide
and propylene oxide; and salts of mono- and di-alkylphosphate
esters; and also further substances described e.g. in "McCutcheon's
Detergents and Emulsifiers Annual" MC Publishing Corp., Ridgewood
N.J., 1981.
[0123] Further adjuvants that can usually be used in pesticidal
formulations include crystallization inhibitors, viscosity
modifiers, suspending agents, dyes, anti-oxidants, foaming agents,
light absorbers, mixing auxiliaries, antifoams, complexing agents,
neutralizing or pH-modifying substances and buffers, corrosion
inhibitors, fragrances, wetting agents, take-up enhancers,
micronutrients, plasticisers, glidants, lubricants, dispersants,
thickeners, antifreezes, microbicides, and also liquid and solid
fertilizers.
[0124] The compositions according to the invention can additionally
include an additive comprising an oil of vegetable or animal
origin, a mineral oil, alkyl esters of such oils or mixtures of
such oils and oil derivatives. The amount of oil additive in the
composition according to the invention is generally from 0.01 to
10%, based on the spray mixture. For example, the oil additive can
be added to the spray tank in the desired concentration after the
spray mixture has been prepared. Preferred oil additives comprise
mineral oils or an oil of vegetable origin, for example rapeseed
oil, olive oil or sunflower oil, emulsified vegetable oil, such as
AMIGO.RTM. (Rhone-Poulenc Canada Inc.), alkyl esters of oils of
vegetable origin, for example the methyl derivatives, or an oil of
animal origin, such as fish oil or beef tallow. A preferred
additive contains, for example, as active components essentially
80% by weight alkyl esters of fish oils and 15% by weight
methylated rapeseed oil, and also 5% by weight of customary
emulsifiers and pH modifiers. Especially preferred oil additives
comprise alkyl esters of C.sub.8-C.sub.22 fatty acids, especially
the methyl derivatives of C.sub.12-C.sub.18 fatty acids, for
example the methyl esters of lauric acid, palmitic acid and oleic
acid, being of importance. Those esters are known as methyl laurate
(CAS-111-82-0), methyl palmitate (CAS-112-39-0) and methyl oleate
(CAS-112-62-9). A preferred fatty acid methyl ester derivative is
Emery.RTM. 2230 and 2231 (Cognis GmbH). Those and other oil
derivatives are also known from the Compendium of Herbicide
Adjuvants, 5th Edition, Southern Illinois University, 2000.
[0125] The application and action of the oil additives can be
further improved by combination with surface-active substances,
such as non-ionic, anionic or cationic surfactants. Examples of
suitable anionic, non-ionic and cationic surfactants are listed on
pages 7 and 8 of WO 97/34485. Preferred surface-active substances
are anionic surfactants of the dodecylbenzylsulfonate type,
especially the calcium salts thereof, and also non-ionic
surfactants of the fatty alcohol ethoxylate type. Special
preference is, given to ethoxylated C.sub.12-C.sub.22 fatty
alcohols having a degree of ethoxylation of from 5 to 40. Examples
of commercially available surfactants are the Genapol types
(Clariant AG). Also preferred are silicone surfactants, especially
polyalkyl-oxide-modified heptamethyltriloxanes which are
commercially available e.g. as Silwet L-77.RTM., and also
perfluorinated surfactants. The concentration of the surface-active
substances in relation to the total additive is generally from 1 to
30% by weight. Examples of oil additives consisting of mixtures of
oil or mineral oils or derivatives thereof with surfactants are
Edenor ME SU.RTM., Turbocharge.RTM. (Syngenta AG, CH) or ActipronC
(BP Oil UK Limited, GB).
[0126] If desired, it is also possible for the mentioned
surface-active substances to be used in the formulations on their
own, that is to say without oil additives.
[0127] Furthermore, the addition of an organic solvent to the oil
additive/surfactant mixture may contribute to an additional
enhancement of action. Suitable solvents are, for example,
Solvesso.RTM. (ESSO) or Aromatic Solvent.RTM. (Exxon Corporation).
The concentration of such solvents can be from 10 to 80% by weight
of the total weight. Oil additives that are present in admixture
with solvents are described, for example, in U.S. Pat. No.
4,834,908. A commercially available oil additive disclosed therein
is known by the name MERGE.RTM. (BASF Corporation). A further oil
additive that is preferred according to the invention is SCORE.RTM.
(Syngenta Crop Protection Canada).
[0128] In addition to the oil additives listed above, for the
purpose of enhancing the action of the compositions according to
the invention it is also possible for formulations of
alkylpyrrolidones (e.g. Agrimax.RTM.) to be added to the spray
mixture. Formulations of synthetic lattices, e.g. polyacrylamide,
polyvinyl compounds or poly-1-p-menthene (e.g. Bond.RTM.,
Courier.RTM. or Emerald.RTM.) may also be used. It is also possible
for solutions that contain propionic acid, for example Eurogkem
Pen-e-Trate.RTM., to be added to the spray mixture as
action-enhancing agent.
[0129] The herbicidal compositions generally comprise from 0.1 to
99% by weight, especially from 0.1 to 95% by weight, compounds of
formula (I) and from 1 to 99.9% to by weight of a formulation
adjuvant which preferably includes from 0 to 25% by weight of a
surface-active substance. Whereas commercial products will
preferably be formulated as concentrates, the end user will
normally employ dilute formulations.
[0130] The rates of application of compounds of formula (I) may
vary within wide limits and depend on the nature of the soil, the
method of application (pre- or post-emergence; seed dressing;
application to the seed furrow; no tillage application etc.), the
crop plant, the grass or weed to be controlled, the prevailing
climatic conditions, and other factors governed by the method of
application, the time of application and the target crop. The
compounds of formula (I) according to the invention are generally
applied at a rate of from 10 to 2000 g/ha, especially from 50 to
1000 g/ha.
[0131] Preferred formulations have especially the following
compositions (%=percent by weight):
Emulsifiable Concentrates:
[0132] active ingredient: 1 to 95%, preferably 60 to 90%
surface-active agent: 1 to 30%, preferably 5 to 20% liquid carrier:
1 to 80%, preferably 1 to 35%
Dusts:
[0133] active ingredient: 0.1 to 10%, preferably 0.1 to 5% solid
carrier: 99.9 to 90%, preferably 99.9 to 99%
Suspension Concentrates:
[0134] active ingredient: 5 to 75%, preferably 10 to 50% water: 94
to 24%, preferably 88 to 30% surface-active agent: 1 to 40%,
preferably 2 to 30%
Wettable Powders:
[0135] active ingredient: 0.5 to 90%, preferably 1 to 80%
surface-active agent: 0.5 to 20%, preferably 1 to 15% solid
carrier: 5 to 95%, preferably 15 to 90%
Granules:
[0136] active ingredient: 0.1 to 30%, preferably 0.1 to 15% solid
carrier: 99.5 to 70%, preferably 97 to 85% The following Examples
further illustrate, but do not limit, the invention.
Formulation Examples for Herbicides of Formula (I) (%=% by
Weight)
TABLE-US-00002 [0137] F1. Emulsifiable concentrates a) b) c) d)
active ingredient 5% 10% 25% 50% calcium dodecylbenzenesulfonate 6%
8% 6% 8% castor oil polyglycol ether 4% -- 4% 4% (36 mol of
ethylene oxide) octylphenol polyglycol ether -- 4% -- 2% (7-8 mol
of ethylene oxide) NMP -- -- 10% 20% arom. hydrocarbon mixture 85%
78% 55% 16% C.sub.9-C.sub.12
Emulsions of any desired concentration can be obtained from such
concentrates by dilution with water.
TABLE-US-00003 F2. Solutions a) b) c) d) active ingredient 5% 10%
50% 90% 1-methoxy-3-(3-methoxy- -- 20% 20% -- propoxy)-propane
polyethylene glycol 20% 10% -- -- MW 400 NMP -- -- 30% 10% arom.
hydrocarbon 75% 60% -- -- mixture C.sub.9-C.sub.12
The solutions are suitable for use in the form of microdrops.
TABLE-US-00004 F3. Wettable powders a) b) c) d) active ingredient
5% 25% 50% 80% sodium lignosulfonate 4% -- 3% -- sodium lauryl
sulfate 2% 3% -- 4% sodium -- 6% 5% 6% diisobutylnaphthalene-
sulfonate octylphenol polyglycol -- 1% 2% -- ether (7-8 mol of
ethylene oxide) highly dispersed silicic acid 1% 3% 5% 10% kaolin
88% 62% 35% --
The active ingredient is mixed thoroughly with the adjuvants and
the mixture is thoroughly ground in a suitable mill, affording
wettable powders which can be diluted with water to give
suspensions of any desired concentration.
TABLE-US-00005 F4. Coated granules a) b) c) active ingredient 0.1%
5% 15% highly dispersed silicic acid 0.9% 2% 2% inorganic carrier
99.0% 93% 83% (diameter 0.1-1 mm) e.g. CaCO.sub.3 or SiO.sub.2
The active ingredient is dissolved in methylene chloride and
applied to the carrier by spraying, and the solvent is then
evaporated off in vacuo.
TABLE-US-00006 F5. Coated granules a) b) c) active ingredient 0.1%
5% 15% polyethylene glycol MW 200 1.0% 2% 3% highly dispersed
silicic acid 0.9% 1% 2% inorganic carrier 98.0% 92% 80% (diameter
0.1-1 mm) e.g. CaCO.sub.3 or SiO.sub.2
The finely ground active ingredient is uniformly applied, in a
mixer, to the carrier moistened with polyethylene glycol. Non-dusty
coated granules are obtained in this manner.
TABLE-US-00007 F6. Extruder granules a) b) c) d) active ingredient
0.1% 3% 5% 15% sodium lignosulfonate 1.5% 2% 3% 4%
carboxymethylcellulose 1.4% 2% 2% 2% kaolin 97.0% 93% 90% 79%
The active ingredient is mixed and ground with the adjuvants, and
the mixture is moistened with water. The mixture is extruded and
then dried in a stream of air.
TABLE-US-00008 F7. Dusts a) b) c) active ingredient 0.1% 1% 5%
talcum 39.9% 49% 35% kaolin 60.0% 50% 60%
Ready-to-use dusts are obtained by mixing the active ingredient
with the carriers and grinding the mixture in a suitable mill.
TABLE-US-00009 F8. Suspension concentrates a) b) c) d) active
ingredient 3% 10% 25% 50% ethylene glycol 5% 5% 5% 5% nonylphenol
polyglycol ether -- 1% 2% -- (15 mol of ethylene oxide) sodium
lignosulfonate 3% 3% 4% 5% carboxymethylcellulose 1% 1% 1% 1% 37%
aqueous formaldehyde 0.2% 0.2% 0.2% 0.2% solution silicone oil
emulsion 0.8% 0.8% 0.8% 0.8% water 87% 79% 62% 38%
The finely ground active ingredient is intimately mixed with the
adjuvants, giving a suspension concentrate from which suspensions
of any desired concentration can be obtained by dilution with
water.
[0138] The invention relates to a method of controlling plants
which comprises applying to the plants or to the locus thereof a
herbicidally effective amount of a compound of formula (I).
[0139] The invention also relates to a method of inhibiting plant
growth which comprises applying to the plants or to the locus
thereof a herbicidally effective amount of a compound of formula
(I).
[0140] The invention also relates to a method of selectively
controlling grasses and weeds in crops of useful plants which
comprises applying to the useful plants or locus thereof or to the
area of cultivation a herbicidally effective amount of a compound
of formula (I).
[0141] Crops of useful plants in which the composition according to
the invention can be used include perennial crops, such as citrus
fruit, grapevines, nuts, oil palms, olives, pome fruit, stone fruit
and rubber, and annual arable crops, such as cereals, for example
barley and wheat, cotton, oilseed rape, maize, rice, soy beans,
sugar beet, sugar cane, sunflowers, ornamentals and vegetables,
especially cereals, maize and soy beans.
[0142] The grasses and weeds to be controlled may be both
monocotyledonous species, for example Agrostis, Alopecurus, Avena,
Bromus, Cyperus, Digitaria, Echinochloa, Lolium, Monochoria,
Rottboellia, Sagittaria, Scirpus, Setaria, Sida and Sorghum, and
dicotyledonous species, for example Abutilon, Amaranthus,
Chenopodium, Chrysanthemum, Galium, Ipomoea, Nasturtium, Sinapis,
Solanum, Stellaria, Veronica, Viola and Xanthium.
[0143] Crops are to be understood as also including those crops
which have been rendered tolerant to herbicides or classes of
herbicides (e.g. auxins or ALS-, GS-, EPSPS-, PPO- and
HPPD-inhibitors) by conventional methods of breeding or by genetic
engineering. An example of a crop that has been rendered tolerant
to imidazolinones, e.g. imazamox, by conventional methods of
breeding is Clearfield.RTM. summer rape (canola). Examples of crops
that have been rendered tolerant to herbicides by genetic
engineering methods include e.g. glyphosate- and
glufosinate-resistant maize varieties commercially available under
the trade names RoundupReady.RTM. and LibertyLink.RTM..
[0144] Crops are also to be understood as being those which have
been rendered resistant to harmful insects by genetic engineering
methods, for example Bt maize (resistant to European corn borer),
Bt cotton (resistant to cotton boll weevil) and also Bt potatoes
(resistant to Colorado beetle). Examples of Bt maize are the Bt 176
maize hybrids of NK.RTM. (Syngenta Seeds). The Bt toxin is a
protein that is formed naturally by Bacillus thuringiensis soil
bacteria. Examples of toxins, or transgenic plants able to
synthesize such toxins, are described in EP-A-451 878, EP-A-374
753, WO 93/07278, WO 95/34656, WO 03/052073 and EP-A-427 529.
Examples of transgenic plants comprising one or more genes that
code for an insecticidal resistance and express one or more toxins
are KnockOut.RTM. (maize), Yield Gard.RTM. (maize), NuCOTIN33B.RTM.
(cotton), Bollgarde.RTM. (cotton), NewLeaf.RTM. (potatoes),
NatureGard.RTM. and Protexcta.RTM.. Plant crops or seed material
thereof can be both resistant to herbicides and, at the same time,
resistant to insect feeding ("stacked" transgenic events). For
example, seed can have the ability to express an insecticidal Cry3
protein while at the same time being tolerant to glyphosate.
[0145] Crops are also to be understood as being those which are
obtained by conventional methods of breeding or genetic engineering
and contain so-called output traits (e.g. improved storage
stability, higher nutritional value and improved flavor).
[0146] Areas under cultivation include land on which the crop
plants are already growing and land intended for cultivation with
those crop plants. The compounds of the invention can be applied
before weeds emerge (pre-emergence application) or after weeds
emerge (post-emergence application), and are particularly effective
when applied post-emergence.
[0147] The compounds of formula (I) according to the invention can
also be used in combination with one or more further herbicides. In
particular, the following mixtures of the compound of formula (I)
are important:
[0148] Mixtures of a compound of formula (I) with a synthetic auxin
(e.g. compound of formula (I)+clopyralid (162), compound of formula
(I)+2,4-D (211), compound of formula (I)+dicamba (228), compound of
formula (I)+diphenamid (274), compound of formula (I)+MCPA (499),
compound of formula (I)+quinclorac (712), or compound of formula
(I)+aminopyralid (CAS RN 150114-71-9)).
[0149] Mixtures of a compound of formula (I) with diflufenzopyr
(252).
[0150] Mixtures of a compound of formula (I) with an acetanilide
(e.g. compound of formula (I)+acetochlor (5), compound of formula
(I)+dimethenamid (260), compound of formula (I)+metolachlor (548),
compound of formula (I)+S-metolachlor (549), or compound of formula
(I)+pretilachlor (656)).
[0151] Mixtures of a compound of formula (I) with flamprop-M
(355).
[0152] Mixtures of a compound of formula (I) with flufenacet (BAY
FOE 5043) (369).
[0153] Mixtures of a compound of formula (I) with pyroxasulfone
(CAS RN 447399-55-5).
[0154] Mixtures of a compound of formula (I) with an HPPD inhibitor
(e.g. compound of formula (I)+isoxaflutole (479), compound of
formula (I)+mesotrione (515), compound of formula (I)+pyrasulfotole
(CAS RN 365400-11-9), compound of formula (I)+sulcotrione (747),
compound of formula (I)+tembotrione (CAS RN 335104-84-2), compound
of formula (I)+topramezone (CAS RN 210631-68-8), compound of
formula
(I)+4-hydroxy-3-[[2-[(2-methoxyethoxy)methyl]-6-(trifluoromethyl)-3-pyrid-
inyl]carbonyl]-bicyclo[3.2.1]oct-3-en-2-one (CAS RN 352010-68-5),
or compound of formula
(I)+4-hydroxy-3-[[2-(3-methoxypropyl)-6-(difluoromethyl)-3-pyridinyl]carb-
onyl]-bicyclo[3.2.1]oct-3-en-2-one (CAS RN 894355-80-7)).
[0155] Mixtures of a compound of formula (I) with a triazine (e.g.
compound of formula (I)+atrazine (37), or compound of formula
(I)+terbuthylazine (775)).
[0156] Mixtures of a compound of formula (I) with a triazine and an
HPPD inhibitor (e.g. compound of formula (I)+triazine+isoxaflutole,
compound of formula (I)+triazine+mesotrione, compound of formula
(I)+triazine+pyrasulfotole, compound of formula
(I)+triazine+sulcotrione, compound of formula
(I)+triazine+tembotrione, compound of formula
(I)+triazine+topramezone, compound of formula
(I)+triazine+4-hydroxy-3-[[2-[(2-methoxyethoxy)methyl]-6-(trifluoromethyl-
)-3-pyridinyl]carbonyl]-bicyclo[3.2.1]oct-3-en-2-one, or compound
of formula
(I)+triazine+4-hydroxy-3-[[2-(3-methoxypropyl)-6-(difluoromethyl)-
-3-pyridinyl]carbonyl]-bicyclo[3.2.1]oct-3-en-2-one).
[0157] Mixtures of a compound of formula (I) with glyphosate
(419).
[0158] Mixtures of a compound of formula (I) with glyphosate and an
HPPD inhibitor (e.g. compound of formula
(I)+glyphosate+isoxaflutole, compound of formula
(I)+glyphosate+mesotrione, compound of formula
(I)+glyphosate+pyrasulfotole, compound of formula
(I)+glyphosate+sulcotrione, compound of formula
(I)+glyphosate+tembotrione, compound of formula
(I)+glyphosate+topramezone, compound of formula
(I)+glyphosate+4-hydroxy-3-[[2-[(2-methoxyethoxy)methyl]-6-(trifluorometh-
yl)-3-pyridinyl]carbonyl]-bicyclo[3.2.1]oct-3-en-2-one, or compound
of formula
(I)+glyphosate+4-hydroxy-3-[[2-(3-methoxypropyl)-6-(difluoromethy-
l)-3-pyridinyl]carbonyl]-bicyclo[3.2.1]oct-3-en-2-one).
[0159] Mixtures of a compound of formula (I) with
glufosinate-ammonium (418).
[0160] Mixtures of a compound of formula (I) with
glufosinate-ammonium and an HPPD inhibitor (e.g. compound of
formula (I)+glufosinate-ammonium+isoxaflutole, compound of formula
(I)+glufosinate-ammonium+mesotrione, compound of formula
(I)+glufosinate-ammonium+pyrasulfotole, compound of formula
(I)+glufosinate-ammonium+sulcotrione, compound of formula
(I)+glufosinate-ammonium+tembotrione, compound of formula
(I)+glufosinate-ammonium+topramezone, compound of formula
(I)+glufosinate-ammonium+4-hydroxy-3-[[2-[(2-methoxyethoxy)methyl]-6-(tri-
fluoromethyl)-3-pyridinyl]carbonyl]-bicyclo[3.2.1]oct-3-en-2-one,
or compound of formula
(I)+glufosinate-ammonium+4-hydroxy-3-[[2-(3-methoxypropyl)-6-(difluoromet-
hyl)-3-pyridinyl]carbonyl]-bicyclo[3.2.1]oct-3-en-2-one).
[0161] Mixtures of a compound of formula (I) with an ALS or an AHAS
inhibitor (e.g. compound of formula (I)+bensulfuron-methyl (64),
compound of formula (I)+chlorimuron-ethyl (135), compound of
formula (I)+cloransulam-methyl (164), compound of formula
(I)+florasulam (359), compound of formula (I)+flucarbazone-sodium
(364), compound of formula (I)+imazamox (451), compound of formula
(I)+imazapyr (453), compound of formula (I)+imazethapyr (455),
compound of formula (I)+iodosulfuron-methyl-sodium (466), compound
of formula (I)+mesosulfuron-methyl (514), compound of formula
(I)+nicosulfuron (577), compound of formula (I)+penoxsulam (622),
compound of formula (I)+pyroxsulam (triflosulam) (CAS RN
422556-08-9), compound of formula (I)+thifensulfuron-methyl
(thiameturon-methyl) (795), compound of formula (I)+triasulfuron
(817), compound of formula (I)+tribenuron-methyl (822), compound of
formula (I)+trifloxysulfuron-sodium (833), compound of formula
(I)+thiencarbazone
(4-[(4,5-dihydro-3-methoxy-4-methyl-5-oxo-1H-1,2,4-triazol-1-yl)carbonyls-
ulfamoyl]-5-methylthiophene-3-carboxylic acid, BAY636)), or
compound of formula (I)+thiencarbazone-methyl (methyl
4-[(4,5-dihydro-3-methoxy-4-methyl-5-oxo-1H-1,2,4-triazol-1-yl)carbonylsu-
lfamoyl]-5-methylthiophene-3-carboxylate, CAS RN 317815-83-1,
BAY636-methyl)).
[0162] Mixtures of a compound of formula (I) with a PPO inhibitor
(e.g. compound of formula (I)+acifluorfen-sodium (7), compound of
formula (I)+butafenacil (101), compound of formula
(I)+carfentrazone-ethyl (121), compound of formula
(I)+cinidon-ethyl (152), compound of formula (I)+flumioxazin (376),
compound of formula (I)+fomesafen (401), compound of formula (I)
lactofen (486), or compound of formula
(I)+[3-[2-chloro-4-fluoro-5-(1-methyl-6-trifluoromethyl-2,4-dioxo-1,2,3,4-
-tetrahydropyrimidin-3-yl)phenoxy]-2-pyridyloxy]acetic acid ethyl
ester) (CAS RN 353292-31-6)).
[0163] Mixtures of a compound of formula (I) with an ACCase
inhibitor (e.g. compound of formula (I)+butroxydim (106), compound
of formula (I)+clethodim (155), compound of formula
(I)+clodinafop-propargyl (156), compound of formula (I)+cycloxydim
(190), compound of formula (I)+cyhalofop-butyl (195), compound of
formula (I)+diclofop-methyl (238), compound of formula
(I)+fenoxaprop-P-ethyl (339), compound of formula
(I)+fluazifop-butyl (361), compound of formula
(I)+fluazifop-P-butyl (362), compound of formula (I)+haloxyfop
(427), compound of formula (I)+haloxyfop-P (428), compound of
formula (I)+propaquizafop (670), compound of formula (I)+quizalofop
(717), compound of formula (I)+quizalofop-P (718), compound of
formula (I)+sethoxydim (726), compound of formula (I)+tepraloxydim
(771), compound of formula (I)+tralkoxydim (811)), or compound of
formula (I)+pinoxaden (CAS RN 243973-20-8).
[0164] Mixtures of a compound of formula (I) with prosulfocarb
(683), or a compound of formula (I) with tri-allate (816).
[0165] Mixtures of a compound of formula (I) with bromoxynil (95),
a compound of formula (I) with chloridazon (134), a compound of
formula (I) with chlorotoluron (143), a compound of formula (I)
with diuron (281), or a compound of formula (I) with metribuzin
(554).
[0166] Mixtures of a compound of formula (I) with clomazone (159),
a compound of formula (I) with diflufenican (251), a compound of
formula (I) with fluorochloridone (389), or a compound of formula
(I) with flurtamone (392).
[0167] Mixtures of a compound of formula (I) with pendimethalin
(621) or a compound of formula (I) with trifluralin (836).
[0168] Mixtures of a compound of formula (I) with difenzoquat
metilsulfate (248).
[0169] Mixtures of a compound of formula (I) with diquat dibromide
(276).
[0170] Mixtures of a compound of formula (I) with paraquat
dichloride (614).
[0171] The mixing partners of the compound of formula (I) may also
be in the form of esters or salts, as mentioned e.g. in The
Pesticide Manual, 13.sup.th Edition (BCPC), 2003. The reference to
glufosinate-ammonium also applies to glufosinate, the reference to
cloransulam-methyl also applies to cloransulam, the reference to
dimethenamid also applies to dimethenamid-P, the reference to
flamprop-M also applies to flamprop, and the reference to
pyrithiobac-sodium also applies to pyrithiobac, etc.
[0172] The mixing ratio of the compound of formula (I) to the
mixing partner is preferably from 1:100 to 1000:1.
[0173] The mixtures can advantageously be used in the
above-mentioned formulations (in which case "active ingredient"
relates to the respective mixture of compound of formula (I) with
the mixing partner).
[0174] Additionally, one or more of the following herbicides or
plant growth regulators can be used in combination with a compound
of formula (I) according to the invention or in combination with a
mixture as described above: aclonifen (8), acrolein (10), alachlor
(14), alloxydim (18), ametryn (20), amicarbazone (21),
amidosulfuron (22), aminocyclopyrachlor (CAS RN 858956-08-8),
amitrole (aminotriazole) (25), ammonium sulfamate (26), anilofos
(31), asulam (36), aviglycine (39), azafenidin (CAS RN 68049-83-2),
azimsulfuron (43), BAS 800H (CAS RN 372137-35-4), beflubutamid
(55), benazolin (57), bencarbazone (CAS RN 173980-17-1),
benfluralin (59), benfuresate (61), bensulide (65), bentazone (67),
benzfendizone (CAS RN 158755-95-4), benzobicyclon (69), benzofenap
(70), bilanafos (bialaphos) (77), bispyribac-sodium (82), borax
(86), bromacil (90), bromobutide (93), bromofenoxim (CAS RN
13181-17-4), butachlor (100), butamifos (102), butralin (105),
butylate (108), cafenstrole (110), carbetamide (117), chlorbromuron
(CAS RN 13360-45-7), chlorflurenol-methyl (133), chloroacetic acid
(138), chlorpropham (144), chlorsulfuron (147), chlorthal-dimethyl
(148), cinmethylin (153), cinosulfuron (154), clomeprop (160),
cumyluron (180), cyanamide (182), cyanazine (183), cyclanilide
(186), cycloate (187), cyclosulfamuron (189), daimuron (213),
dalapon (214), dazomet (216), desmedipham (225), desmetryn (CAS RN
1014-69-3), dichlobenil (229), dichlorprop (234), dichlorprop-P
(235), diclosulam (241), dimefuron (256), dimepiperate (257),
dimethachlor (258), dimethametryn (259), dimethipin (261),
dimethylarsinic acid (264), dinitramine (268), dinoterb (272),
dipropetryn (CAS RN 4147-51-7), dithiopyr (280), DNOC (282), DSMA
(CAS RN 144-21-8), endothal (295), EPTC (299), esprocarb (303),
ethalfluralin (305), ethametsulfuron-methyl (306), ethephon (307),
ethofumesate (311), ethoxyfen (CAS RN 188634-90-4), ethoxyfen-ethyl
(CAS RN 131086-42-5), ethoxysulfuron (314), etobenzanid (318),
fentrazamide (348), ferrous sulfate (353), flazasulfuron (356),
fluazolate (isopropazol) (CAS RN 174514-07-9), flucetosulfuron (CAS
RN 412928-75-7), fluchloralin (365), flufenpyr-ethyl (371),
flumetralin (373), flumetsulam (374), flumiclorac-pentyl (375),
flumipropyn (flumipropin) (CAS RN 84478-52-4), fluometuron (378),
fluoroglycofen-ethyl (380), flupoxam (CAS RN 119126-15-7),
flupropacil (CAS RN 120890-70-2), flupropanate (383),
flupyrsulfuron-methyl-sodium (384), flurenol (387), fluridone
(388), fluoroxypyr (390), fluthiacet-methyl (395), foramsulfuron
(402), fosamine (406), halosulfuron-methyl (426), HC-252 (429),
hexazinone (440), imazamethabenz-methyl (450), imazapic (452),
imazaquin (454), imazosulfuron (456), indanofan (462), ioxynil
(467), isoproturon (475), isouron (476), isoxaben (477),
isoxachlortole (CAS RN 141112-06-3), isoxapyrifop (CAS RN
87757-18-4), karbutilate (482), lenacil (487), linuron (489),
MCPA-thioethyl (500), MCPB (501), mecoprop (503), mecoprop-P (504),
mefenacet (505), mefluidide (507), metam (519), metamifop
(mefluoxafop) (520), metamitron (521), metazachlor (524),
methabenzthiazuron (526), methazole (CAS RN 20354-26-1),
methylarsonic acid (536), 1-methylcyclopropene (538), methyldymron
(539), methyl isothiocyanate (543), metobenzuron (547),
metobromuron (CAS RN 3060-89-7), metosulam (552), metoxuron (553),
metsulfuron-methyl (555), MK-616 (559), molinate (560), monolinuron
(562), MSMA (CAS RN 2163-80-6), naproanilide (571), napropamide
(572), naptalam (573), neburon (574), nipyraclofen (CAS RN
99662-11-0), n-methyl-glyphosate, nonanoic acid (583), norflurazon
(584), oleic acid (fatty acids) (593), orbencarb (595),
orthosulfamuron (CAS RN 213464-77-8), oryzalin (597), oxadiargyl
(599), oxadiazon (600), oxasulfuron (603), oxaziclomefone (604),
oxyfluorfen (610), pebulate (617), pentachlorophenol (623),
pentanochlor (624), pentoxazone (625), pethoxamid (627), petrolium
oils (628), phenmedipham (629), picloram (645), picolinafen (646),
piperophos (650), primisulfuron-methyl (657), prodiamine (661),
profluazol (CAS RN 190314-43-3), profoxydim (663), prohexadione
calcium (664), prometon (665), prometryn (666), propachlor (667),
propanil (669), propazine (672), propham (674), propisochlor (667),
propoxycarbazone-sodium (procarbazone-sodium) (679), propyzamide
(681), prosulfuron (684), pyraclonil (pyrazogyl) (CAS RN
158353-15-2), pyraflufen-ethyl (691), pyrazolynate (692),
pyrazosulfuron-ethyl (694), pyrazoxyfen (695), pyribenzoxim (697),
pyributicarb (698), pyridafol (CAS RN 40020-01-7), pyridate (702),
pyriftalid (704), pyriminobac-methyl (707), pyrimisulfan (CAS RN
221205-90-9), pyrithiobac-sodium (709), quinmerac (713),
quinoclamine (714), rimsulfuron (721), sequestrene, siduron (727),
simazine (730), simetryn (732), sodium chlorate (734),
sulfentrazone (749), sulfometuron-methyl (751), sulfosate (CAS RN
81591-81-3), sulfosulfuron (752), sulfuric acid (755), tar oils
(758), TCA-sodium (760), tebutam (CAS RN 35256-85-0), tebuthiuron
(765), tefuryltrione (CAS RN 473278-76-1), terbacil (772),
terbumeton (774), terbutryn (776), thenylchlor (789), thidiazimin
(CAS RN 123249-43-4), thiazafluoron (CAS RN 25366-23-8), thiazopyr
(793), thiobencarb (797), tiocarbazil (807), triaziflam (819),
triclopyr (827), trietazine (831), triflusulfuron-methyl (837),
trihydroxytriazine (CAS RN 108-80-5), trinexapac-ethyl (CAS RN
95266-40-3), tritosulfuron (843),
N-[(1R,2S)-2,6-dimethyl-2,3-dihydro-1H-inden-1-yl]-6-(1-fluoroethyl)-1,3,-
5-triazine-2,4-diamine (CAS RN 950782-86-2),
1-(2-chloro-6-propylimidazo[1,2-b]pyridazin-3-ylsulfonyl)-3-(4,6-dimethox-
ypyrimidin-2-yl)urea (CAS RN 570415-88-2), and
5-(2,6-difluoro-benzyloxymethyl)-5-methyl-3-(3-methyl-thiophen-2-yl)-4,5--
dihydro-isoxazole (CAS RN 403640-27-7).
[0175] The mixing partners of the compound of formula (I) may also
be in the form of esters or salts, as mentioned e.g. in The
Pesticide Manual, 13.sup.th Edition (BCPC), 2003. The reference to
acifluorfen-sodium also applies to acifluorfen, and the reference
to bensulfuron-methyl also applies to bensulfuron, etc.
[0176] The mixing ratio of the compound of formula (I) to the
mixing partner is preferably from 1:100 to 1000:1.
[0177] The mixtures can advantageously be used in the
above-mentioned formulations (in which case "active ingredient"
relates to the respective mixture of compound of formula (I) with
the mixing partner).
[0178] The compounds of formula (I) according to the invention can
also be used in combination with one or more safeners. Likewise,
mixtures of a compound of formula (I) according to the invention
with one or more further herbicides can also be used in combination
with one or more safeners. The term "safener" as used herein means
a chemical that when used in combination with a herbicide reduces
the undesirable effects of the herbicide on non-target organisms,
for example, a safener protects crops from injury by herbicides but
does not prevent the herbicide from killing the weeds. The safeners
can be AD-67 (11), benoxacor (63), cloquintocet-mexyl (163),
cyometrinil (CAS RN 78370-21-5), cyprosulfamide (CAS RN
221667-31-8), dichlormid (231), dicyclonon (CAS RN 79260-71-2),
fenchlorazole-ethyl (331), fenclorim (332), flurazole (386),
fluxofenim (399), furilazole (413) and the corresponding R isomer,
isoxadifen-ethyl (478), mefenpyr-diethyl (506),
2-methoxy-N-[[4-[[methylamino)carbonyl]amino]-phenyl]sulfonyl]-benzamide
(CAS RN 129531-12-0), naphthalic anhydride (CAS RN 81-84-5), and
oxabetrinil (598). Particularly preferred are mixtures of a
compound of formula (I) with benoxacor and a compound of formula
(I) with cloquintocet-mexyl.
[0179] The safeners of the compound of formula (I) may also be in
the form of esters or salts, as mentioned e.g. in The Pesticide
Manual, 13.sup.th Edition (BCPC), 2003. The reference to
cloquintocet-mexyl also applies to cloquintocet, and the reference
to fenchlorazole-ethyl also applies to fenchlorazole, etc.
[0180] Preferably the mixing ratio of compound of formula (I) to
safener is from 100:1 to 1:10, especially from 20:1 to 1:1.
[0181] The mixtures can advantageously be used in the
above-mentioned formulations (in which case "active ingredient"
relates to the respective mixture of compound of formula (I) with
the safener). It is possible that the safener and a compound of
formula (I) and one or more additional herbicide(s), if any, are
applied simultaneously. For example, the safener, a compound of
formula (I) and one or more additional herbicide(s), if any, might
be applied to the locus pre-emergence or might be applied to the
crop post-emergence. It is also possible that the safener and a
compound of formula (I) and one or more additional herbicide(s), if
any, are applied sequentially. For example, the safener might be
applied before sowing the seeds as a seed treatment and a compound
of formula (I) and one or more additional herbicides, if any, might
be applied to the locus pre-emergence or might be applied to the
crop post-emergence.
[0182] Preferred mixtures of a compound of formula (I) with further
herbicides and safeners include:
[0183] Mixtures of a compound of formula (I) with S-metolachlor and
a safener, particularly benoxacor.
[0184] Mixtures of a compound of formula (I) with isoxaflutole and
a safener.
[0185] Mixtures of a compound of formula (I) with mesotrione and a
safener.
[0186] Mixtures of a compound of formula (I) with sulcotrione and a
safener.
[0187] Mixtures of a compound of formula (I) with a triazine and a
safener.
[0188] Mixtures of a compound of formula (I) with a triazine and
isoxaflutole and a safener.
[0189] Mixtures of a compound of formula (I) with a triazine and
mesotrione and a safener.
[0190] Mixtures of a compound of formula (I) with a triazine and
sulcotrione and a safener.
[0191] Mixtures of a compound of formula (I) with glyphosate and a
safener.
[0192] Mixtures of a compound of formula (I) with glyphosate and
isoxaflutole and a safener.
[0193] Mixtures of a compound of formula (I) with glyphosate and
mesotrione and a safener.
[0194] Mixtures of a compound of formula (I) with glyphosate and
sulcotrione and a safener.
[0195] Mixtures of a compound of formula (I) with
glufosinate-ammonium and a safener.
[0196] Mixtures of a compound of formula (I) with
glufosinate-ammonium and isoxaflutole and a safener.
[0197] Mixtures of a compound of formula (I) with
glufosinate-ammonium and mesotrione and a safener.
[0198] Mixtures of a compound of formula (I) with
glufosinate-ammonium and sulcotrione and a safener.
[0199] Mixtures of a compound of formula (I) with florasulam and a
safener, particularly cloquintocet-mexyl.
[0200] Mixtures of a compound of formula (I) with
clodinafop-propargyl and a safener, particularly
cloquintocet-mexyl.
[0201] Mixtures of a compound of formula (I) with pinoxaden and a
safener, particularly cloquintocet-mexyl.
[0202] Mixtures of a compound of formula (I) with bromoxynil and a
safener, particularly cloquintocet-mexyl.
[0203] The following Examples further illustrate, but do not limit,
the invention.
PREPARATION EXAMPLES
1. Reactions that are Covered by Scheme 1
[0204] Some methanesulfonyl chlorides are commercially available,
for example, (2-bromo-phenyl)-methanesulfonyl chloride,
(2-cyano-phenyl)-methanesulfonyl chloride,
(2,4-dichloro-5-fluoro-phenyl)-methanesulfonyl chloride,
(3,4-dichloro-phenyl)-methanesulfonyl chloride,
(2-nitro-phenyl)-methanesulfonyl chloride,
(2-trifluoromethyl-phenyl)-methanesulfonyl chloride and
(3-trifluoromethyl-phenyl)-methanesulfonyl chloride. Other
methanesulfonyl chlorides were made using the methods according to
Example 1.1-Example 1.4 below.
Example 1.1
Preparation of sodium
(2-chloro-5-trifluoromethyl-phenyl)-methane-sulfonic acid
##STR00024##
[0206] To a solution of 2-chloro-5-trifluoromethyl-benzyl bromide
(10 g) in acetone (20 ml) was added a solution of sodium sulfite
(4.9 g) in water (20 ml). The reaction mixture was heated to reflux
for 3 hours. The reaction mixture was concentrated. The residue was
recrystallised from acetone to give sodium
(2-chloro-5-trifluoromethyl-phenyl)-methane-sulfonic acid as an off
white solid (9.652 g). 1H-NMR (400 MHz, d.sub.6-DMSO): 7.89 (m,
1H), 7.58-7.65 (m, 2H), 3.98 (s, 2H) ppm.
[0207] The following compounds were made using the same method:
[0208] Sodium (2,5-bis-(trifluoromethyl)-phenyl)-methanesulfonic
acid. 1H-NMR (400 MHz, d.sub.6-DMSO): 8.15 (d, 1H), 7.73-7.98 (m,
2H), 3.93 (s, 2H) ppm.
[0209] Sodium (2,6-bis-(trifluoromethyl)-phenyl)-methanesulfonic
acid. 1H-NMR (400 MHz, d.sub.o-DMSO): 7.97 (d, 2H), 7.63-7.67 (m,
1H), 4.26 (s, 2H) ppm.
[0210] Sodium (3-bromo-2-chloro-6-fluoro-phenyl)-methanesulfonic
acid. 1H-NMR (400 MHz, d.sub.6-DMSO): 7.67-7.69 (m, 1H), 7.14-7.17
(m, 1H), 4.01 (s, 2H) ppm.
[0211] Sodium (2-bromo-5-trifluoromethyl-phenyl)-methanesulfonic
acid. 1H-NMR (400 MHz, d.sub.6-DMSO): 7.84 (d, 1H), 7.73-7.75 (m,
1H), 7.42-7.45 (dd, 1H), 3.95 (s, 2H) ppm.
[0212] Sodium (2-chloro-3,6-difluoro-phenyl)-methanesulfonic acid.
The crude compound was used directly for further synthesis.
[0213] Sodium (2-chloro-6-fluoro-3-methoxy-phenyl)-methanesulfonic
acid. The crude compound was used directly for further
synthesis.
[0214] Sodium (2-chloro-6-fluoro-3-methyl-phenyl)-methanesulfonic
acid. The crude compound was used directly for further
synthesis.
[0215] Sodium (2-chloro-5-iodo-phenyl)-methanesulfonic acid. 1H-NMR
(400 MHz, d.sub.6-DMSO): 7.87 (d, 1H), 7.54-7.57 (dd, 1H), 7.18 (d,
1H), 3.84 (s, 2H) ppm.
[0216] Sodium (2-chloro-quinolin-3-yl)-methanesulfonic acid. The
crude compound was used directly for further synthesis.
[0217] Sodium (2-chloro-3-trifluoromethyl-phenyl)-methanesulfonic
acid. 1H-NMR (400 MHz, d.sub.6-DMSO): 7.83 (d, 1H), 7.72 (d, 1H),
7.47 (t, 1H), 4.01 (s, 2H) ppm.
[0218] Sodium (2-chloro-6-trifluoromethyl-phenyl)-methanesulfonic
acid. 1H-NMR (400 MHz, d.sub.6-DMSO): 7.65-7.67 (d, 1H), 7.57-7.59
(d, 1H), 7.35-7.39 (t, 1H), 4.15 (s, 2H) ppm.
[0219] Sodium (4-chloro-2-trifluoromethyl-phenyl)-methanesulfonic
acid. 1H-NMR (400 MHz, d.sub.6-DMSO): 7.83-7.86 (dd, 1H), 7.43 (d,
1H), 7.32-7.34 (d, 1H), 4.05 (s, 2H) ppm.
[0220] Sodium (2,6-dibromo-phenyl)-methanesulfonic acid. 1H-NMR
(400 MHz, d.sub.6-DMSO): 7.59 (d, 2H), 7.05 (t, 1H), 4.21 (s, 2H)
ppm.
[0221] Sodium (2,3-dichloro-6-fluoro-phenyl)-methanesulfonic acid.
The crude compound was used directly for further synthesis.
[0222] Sodium (2,4-dichloro-5-fluoro-phenyl)-methanesulfonic acid.
1H-NMR (400 MHz, d.sub.6-DMSO): 7.73 (d, 1H), 7.55 (d, 1H), 3.88
(s, 2H) ppm.
[0223] Sodium (2,3-dichloro-phenyl)-methanesulfonic acid. 1H-NMR
(400 MHz, d.sub.6-DMSO): 7.43-7.45 (m, 2H), 7.23 (t, 1H), 3.92 (s,
2H) ppm.
[0224] Sodium (2,6-dichloro-phenyl)-methanesulfonic acid. The crude
compound was used directly for further synthesis.
[0225] Sodium
(2,5-dichloro-6-trifluoromethyl-phenyl)-methanesulfonic acid.
1H-NMR (400 MHz, d.sub.6-DMSO): 7.74 (d, 1H), 7.67 (d, 1H), 4.29
(s, 2H) ppm.
[0226] Sodium (2-fluoro-6-trifluoromethyl-phenyl)-methanesulfonic
acid. 1H-NMR (400 MHz, d.sub.6-DMSO): 7.39-7.44 (m, 3H), 3.94 (s,
2H) ppm.
[0227] Sodium (2-iodo-phenyl)-methanesulfonic acid. 1H-NMR (400
MHz, d.sub.5-DMSO): 7.71-7.74 (dd, 1H), 7.48-7.51 (dd, 1H),
7.22-7.26 (dt, 1H), 6.86-6.90 (dt, 1H), 3.85 (s, 2H) ppm.
[0228] Sodium (2,3,6-trichloro-phenyl)-methanesulfonic acid. 1H-NMR
(400 MHz, d.sub.6-DMSO): 7.50 (d, 1H), 7.43 (d, 1H), 4.20 (s, 2H)
ppm.
[0229] Sodium (2-trifluoromethoxy-phenyl)-methanesulfonic acid. The
crude compound was used directly for further synthesis.
[0230] Sodium (2-trifluoromethylthio-phenyl)-methanesulfonic acid.
The crude compound was used directly for further synthesis.
Example 1.2
Preparation of (2-chloro-5-trifluoromethyl-phenyl)-methanesulfonyl
chloride
##STR00025##
[0232] A mixture of sodium
(2-chloro-5-trifluoromethyl-phenyl)-methanesulfonic acid (Example
1.1) (9.4 g) and phosphorous pentachloride (13.5 g) was heated to
80-90.degree. C. for 4 hours. The reaction mixture was
concentrated. The residue was poured onto a mixture of ice and
water and the mixture extracted twice with dichloromethane. The
combined organic extracts were washed with water and brine, dried
over magnesium sulfate and concentrated to give
(2-chloro-5-trifluoromethyl-phenyl)-methanesulfonyl chloride as an
off-white solid (8.480 g). 1H-NMR (400 MHz, CDCl.sub.3): 7.87 (m,
1H), 7.68 (m, 2H), 5.15 (s, 2H) ppm.
[0233] The following compounds were made using the same method:
[0234] (2,5-Bis-(trifluoromethyl)-phenyl)-methanesulfonyl chloride.
1H-NMR (400 MHz, CDCl.sub.3): 8.08 (s, 1H), 7.96 (d, 1H), 7.89 (d,
1H), 5.18 (s, 2H) ppm.
[0235] (2,6-Bis-(trifluoromethyl)-phenyl)-methanesulfonyl chloride.
1H-NMR (400 MHz, CDCl.sub.3): 8.05 (d, 2H), 7.78 (d, 1H), 5.63 (s,
2H) ppm.
[0236] (3-Bromo-2-chloro-6-fluoro-phenyl)-methanesulfonyl chloride.
1H-NMR (400 MHz, CDCl.sub.3): 7.75-7.78 (m, 1H), 7.06-7.09 (m, 1H),
5.25 (s, 2H) ppm.
[0237] (2-Bromo-5-trifluoromethyl-phenyl)-methanesulfonyl chloride.
1H-NMR (400 MHz, CDCl.sub.3): 7.84-7.87 (m, 2H), 7.58-7.61 (m, 1H),
5.18 (s, 2H) ppm.
[0238] (2-Chloro-3,6-difluoro-phenyl)-methanesulfonyl chloride.
1H-NMR (400 MHz, CDCl.sub.3): 7.28-7.34 (m, 1H), 7.12-7.18 (m, 1H),
5.19 (s, 2H) ppm.
[0239] (2-Chloro-6-fluoro-3-methoxy-phenyl)-methanesulfonyl
chloride. 1H-NMR (400 MHz, CDCl.sub.3): 6.98-7.05 (m, 2H), 5.22 (s,
2H), 3.92 (s, 3H) ppm.
[0240] (2-Chloro-6-fluoro-3-methyl-phenyl)-methanesulfonyl
chloride. 1H-NMR (400 MHz, CDCl.sub.3): 7.34-7.37 (m, 1H),
7.04-7.07 (m, 1H), 5.23 (s, 2H), 2.41 (s, 3H) ppm.
[0241] (2-Chloro-5-iodo-phenyl)-methanesulfonyl chloride. 1H-NMR
(400 MHz, CDCl.sub.3): 7.90 (d, 1H), 7.72-7.74 (dd, 1H), 7.25 (d,
1H), 5.03 (s, 2H) ppm.
[0242] (2-Chloro-quinolin-3-yl)-methanesulfonyl chloride. 1H-NMR
(400 MHz, CDCl.sub.3): 8.45 (s, 1H), 8.07 (d, 1H), 7.91 (d, 1H),
7.85 (dt, 1H), 7.66 (dt, 1H), 5.27 (s, 2H) ppm.
[0243] (2-Chloro-3-trifluoromethyl-phenyl)-methanesulfonyl
chloride. 1H-NMR (400 MHz, CDCl.sub.3): 7.76 (d, 1H), 7.66 (d, 1H),
7.41 (t, 1H), 4.87 (s, 2H) ppm.
[0244] (2-Chloro-6-trifluoromethyl-phenyl)-methanesulfonyl
chloride. 1H-NMR (400 MHz, CDCl.sub.3): 7.75-7.77 (d, 1H),
7.73-7.75 (d, 1H), 7.53-7.58 (t, 1H), 5.55 (s, 2H) ppm.
[0245] (4-Chloro-2-trifluoromethyl-phenyl)-methanesulfonyl
chloride. 1H-NMR (400 MHz, CDCl.sub.3): 7.76-7.78 (d, 1H), 7.74 (s,
1H), 7.63-7.65 (d, 1H), 5.10 (s, 2H) ppm.
[0246] (2,6-Dibromo-phenyl)-methanesulfonyl chloride. 1H-NMR (400
MHz, CDCl.sub.3): 7.67 (d, 2H), 7.17 (t, 1H), 5.55 (s, 2H) ppm.
[0247] (2,3-Dichloro-6-fluoro-phenyl)-methanesulfonyl chloride.
1H-NMR (400 MHz, CDCl.sub.3): 7.59-7.62 (m, 1H), 7.12-7.16 (m, 1H),
5.23 (s, 2H) ppm.
[0248] (2,4-Dichloro-5-fluoro-phenyl)-methanesulfonyl chloride.
1H-NMR (400 MHz, CDCl.sub.3): 7.43 (d, 1H), 7.60 (d, 1H), 5.04 (s,
2H) ppm.
[0249] (2,3-Dichloro-phenyl)-methanesulfonyl chloride. 1H-NMR (400
MHz, CDCl.sub.3): 7.51-7.61 (m, 2H), 7.32 (t, 1H), 5.16 (s, 2H)
ppm.
[0250] (2,6-Dichloro-phenyl)-methanesulfonyl chloride. 1H-NMR (400
MHz, CDCl.sub.3): 7.44-7.46 (m, 1H), 7.33-7.38 (m, 1H), 7.19-7.23
(m, 1H), 5.43 (s, 2H) ppm.
[0251] (2,5-Dichloro-6-trifluoromethyl-phenyl)-methanesulfonyl
chloride. 1H-NMR (400 MHz, CDCl.sub.3): 7.67 (d, 1H), 7.56 (d, 1H),
5.54 (s, 2H) ppm.
[0252] (2-Fluoro-6-trifluoromethyl-phenyl)-methanesulfonyl
chloride. 1H-NMR (400 MHz, CDCl.sub.3): 7.59-7.64 (m, 2H),
7.41-7.45 (m, 1H), 5.30 (s, 2H) ppm.
[0253] (2-Iodo-phenyl)-methanesulfonyl chloride. 1H-NMR (400 MHz,
CDCl.sub.3): 7.96-7.98 (m, 1H), 7.62-7.64 (m, 1H), 7.43-7.47 (m,
1H), 7.14-7.17 (m, 1H), 5.16 (s, 2H) ppm.
[0254] (2,3,6-Trichloro-phenyl)-methanesulfonyl chloride. 1H-NMR
(400 MHz, CDCl.sub.3): 7.54 (d, 1H), 7.41 (d, 1H), 5.47 (s, 2H)
ppm.
[0255] (2-Trifluoromethoxy-phenyl)-methanesulfonyl chloride. 1H-NMR
(400 MHz, CDCl.sub.3): 7.61-7.63 (dd, 1H), 7.52-7.54 (dd, 1H),
7.38-7.40 (d, 2H), 4.99 (s, 2H) ppm.
[0256] (2-Trifluoromethylthio-phenyl)-methanesulfonyl chloride.
1H-NMR (400 MHz, CDCl.sub.3): 7.88-7.90 (m, 1H), 7.71-7.73 (m, 1H),
7.55-7.65 (d, 2H), 5.30 (s, 2H) ppm.
Example 1.3
Preparation of thioacetic acid S-(4-bromo-2-trifluoromethyl-benzyl)
ester
##STR00026##
[0258] To a solution of 4-bromo-2-trifluoromethylbenzyl bromide
(2.4 g) in acetone (20 ml) was added potassium thioacetate (1.04
g). The reaction mixture was heated to reflux for 4 hours. The
reaction mixture was allowed to cool to ambient temperature and was
then filtered through a plug of silica gel. Further acetone (30 ml)
was passed through the silica gel (30 ml). The combined filtrate
was concentrated to give thioacetic acid
S-(4-bromo-2-trifluoromethyl-benzyl) ester as a dark liquid (2.275
g). 1H-NMR (400 MHz, CDCl.sub.3): 7.75 (s, 1H), 7.60 (d, 1H), 7.42
(d, 1H), 4.25 (s, 2H), 2.36 (s, 3H) ppm.
[0259] The following compounds were made using the same method:
[0260] Thioacetic acid S-(2,4-bis-(trifluoromethyl)-benzyl) ester.
1H-NMR (400 MHz, CDCl.sub.3): 7.88 (s, 1H), 7.69-7.76 (m, 2H), 4.34
(s, 2H), 2.38 (s, 3H) ppm.
[0261] Thioacetic acid S-(2-chloro-6-fluoro-5-methoxy-benzyl)
ester. 1H-NMR (400 MHz, CDCl.sub.3): 7.09-7.12 (dd, 1H), 6.83 (t,
1H), 4.32 (d, 2H), 3.87 (s, 3H), 2.35 (s, 3H), ppm.
[0262] Thioacetic acid S-(2-chloro-4-iodo-benzyl) ester. 1H-NMR
(400 MHz, CDCl.sub.3): 7.70 (d, 1H), 7.52 (s, 1H), 7.17 (d, 1H),
4.14 (s, 2H), 2.33 (s, 3H) ppm.
[0263] Thioacetic acid S-(3-chloro-5-trifluoromethyl-benzyl) ester.
1H-NMR (400 MHz, CDCl.sub.3): 7.48 (m, 2H), 7.43 (s, 1H), 4.11 (s,
2H), 2.38 (s, 3H) ppm.
[0264] Thioacetic acid S-(5-chloro-2-trifluoromethyl-benzyl) ester.
1H-NMR (400 MHz, CDCl.sub.3): 7.56 (d, 1H), 7.53 (s, 1H), 7.33 (d,
1H), 4.27 (s, 2H), 2.38 (s, 3H) ppm.
[0265] Thioacetic acid S-(2,3-dichloro-6-trifluoromethyl-benzyl)
ester. The crude compound was used directly for further
synthesis.
[0266] Thioacetic acid
S-(3-ethoxycarbonyl-6-trifluoromethyl-pyrid-2-yl) ester. 1H-NMR
(400 MHz, CDCl.sub.3): 8.35 (d, 1H), 7.61 (d, 1H), 4.73 (s, 2H),
4.47 (q, 2H), 2.33 (s, 3H), 1.44 (t, 3H) ppm.
[0267] Thioacetic acid S-(5-methyl-2-trifluoromethyl-benzyl) ester.
The crude compound was used directly for further synthesis.
Example 1.4
Preparation of (4-bromo-2-trifluoromethyl-phenyl)-methanesulfonyl
chloride
##STR00027##
[0269] To a mixture of aqueous hydrochloric acid (2M) (2 ml) and
acetonitrile (10 ml) was added N-chlorosuccinimide ("NCS") (3.9 g)
in portions. To this mixture was added at 20-25.degree. C. added
drop wise a solution of thioacetic acid
S-(4-bromo-2-trifluoromethyl-benzyl) ester (Example 1.3) (2.27 g)
in acetonitrile (3 ml). It was necessary to control the temperature
of the reaction by using an ice bath and regulating the addition
rate of the thioacetic acid S-(4-bromo-2-trifluoromethyl-benzyl)
ester. On completion of the addition the reaction mixture was
stirred at ambient temperature for 30 minutes. The reaction mixture
was partitioned between diethyl ether (50 ml) and aqueous sodium
chloride (12% w/v) (20 ml). The organic layer was washed with
further aqueous sodium chloride (12% w/v) (2.times.20 ml). The
organic layer was concentrated, the residue absorbed onto silica
gel and purified by column chromatography on silica (eluent: 1:1
dichloro-methane/iso-hexane) to give
(4-bromo-2-trifluoromethyl-phenyl)-methanesulfonyl chloride as a
yellow oil (2.225 g). 1H-NMR (400 MHz, CDCl.sub.3): 7.94 (s, 1H),
7.81 (d, 1H), 7.68 (d, 1H), 5.08 (s, 2H) ppm.
[0270] The following compounds were made using the same method:
[0271] (2,4-Bis-(trifluoromethyl)-phenyl)-methanesulfonyl chloride.
1H-NMR (400 MHz, CDCl.sub.3): 8.06 (s, 1H), 7.94-8.01 (m, 2H), 5.19
(s, 2H) ppm.
[0272] (2-Chloro-6-fluoro-5-methoxy-phenyl)-methanesulfonyl
chloride. .sup.1H-NMR (400 MHz, CDCl.sub.3): 7.25-7.28 (dd, 1H),
7.04 (t, 1H), 5.18 (s, 2H), 3.92 (s, 3H) ppm.
[0273] (2-Chloro-4-iodo-phenyl)-methanesulfonyl chloride. 1H-NMR
(400 MHz, CDCl.sub.3): 7.89 (d, 1H), 7.72 (d, 1H), 7.30 (d, 1H),
5.04 (s, 2H) ppm.
[0274] (3-Chloro-5-trifluoromethyl-phenyl)-methanesulfonyl
chloride. 1H-NMR (400 MHz, CDCl.sub.3): 7.75 (s, 1H), 7.69 (s, 1H),
7.65 (s, 1H), 4.88 (s, 2H) ppm.
[0275] (5-Chloro-2-trifluoromethyl-phenyl)-methanesulfonyl
chloride. 1H-NMR (400 MHz, CDCl.sub.3): 7.80 (s, 1H), 7.74 (d, 1H),
7.59 (s, 1H), 5.10 (s, 2H) ppm.
[0276] (2,3-Dichloro-6-trifluoromethyl-phenyl)-methanesulfonyl
chloride. 1H-NMR (400 MHz, CDCl.sub.3): 7.74 (s, 1H), 7.67 (d, 1H),
5.59 (s, 2H) ppm.
[0277]
(3-Ethoxycarbonyl-6-trifluoromethyl-pyrid-2-yl)-methanesulfon-yl
chloride. 1H-NMR (400 MHz, CDCl.sub.3): 8.56 (d, 1H), 7.87 (d, 1H),
5.83 (s, 2H), 4.48 (q, 2H), 1.44 (t, 3H) ppm.
[0278] (5-Methyl-2-trifluoromethyl-phenyl)-methanesulfonyl
chloride. 1H-NMR (400 MHz, CDCl.sub.3): 7.67 (d, 1H), 7.58 (s, 1H),
7.39 (d, 1H), 5.11 (s, 2H), 2.47 (s, 31-1) ppm.
2. Reactions that are Covered by Scheme 2
Example 2.1
Preparation of
3-(2-chloro-5-trifluoromethyl-phenylmethanesulfonyl-amino)-pyrazine-2-car-
boxylic acid methyl ester
##STR00028##
[0280] To a solution of 3-amino-pyrazine-2-carboxylic acid methyl
ester (commercially available) (2.0 g) and
(2-chloro-5-trifluoromethyl-phenyl)-methanesulfonyl chloride
(Example 1.2) (4.2 g) in dichloromethane (32 ml) was added dropwise
pyridine (5.3 ml) over a period of 5 minutes at ambient
temperature. The reaction mixture was stirred at ambient
temperature for 23 hours. Dichloromethane (50 ml) was added to the
reaction mixture and the mixture was washed with aqueous sulfuric
acid (2M) (3.times.30 ml). The phases were separated and the
organic layer was concentrated. The residue was purified by column
chromatography on silica gel (eluent: ethyl acetate/dichloromethane
from 0:10 to 1:9) to give
3-(2-chloro-5-trifluoromethyl-phenylmethanesulfonylamino)-pyrazine-2-carb-
oxylic acid methyl ester as a white solid (4.728 g). 1H-NMR (400
MHz, CDCl.sub.3): 10.30 (s, 1H), 8.59 (s, 1H), 8.47 (s, 1H), 7.77
(bs, 1H), 7.54-7.60 (m, 2H), 5.15 (s, 2H), 4.04 (s, 3H) ppm.
[0281] The following compounds were made using the same method:
[0282]
3-(2,4-Bis-(trifluoromethyl)-phenylmethanesulfonylamino)-pyrazine-2-
-carboxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 10.40
(s, 1H), 8.56 (d, 1H), 8.48 (d, 1H), 7.98-8.01 (m, 2H), 7.88 (d,
1H), 5.21 (s, 2H), 4.06 (s, 3H) ppm.
[0283]
3-(2,5-Bis-(trifluoromethyl)-phenylmethanesulfonylamino)-pyrazine-2-
-carboxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 10.40
(s, 1H), 8.57 (d, 1H), 8.48 (d, 1H), 8.06 (s, 1H), 7.88 (d, 1H),
7.79 (d, 1H), 5.20 (s, 2H), 4.06 (s, 3H) ppm.
[0284]
3-(2,6-Bis-(trifluoromethyl)-phenylmethanesulfonylamino)-pyrazine-2-
-carboxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 10.36
(s, 1H), 8.58 (d, 1H), 8.47 (d, 1H), 8.00 (d, 2H), 7.69 (t, 1H),
5.45 (s, 2H), 4.06 (s, 3H) ppm.
[0285]
3-(3-Bromo-2-chloro-6-fluoro-phenylmethanesulfonylamino)-pyrazine-2-
-carboxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 10.33
(bs, 1H), 8.58 (d, 1H), 8.45 (d, 1H), 7.65-7.67 (m, 1H), 6.95-6.98
(m, 1H), 5.23 (s, 2H), 4.05 (s, 3H) ppm.
[0286] 3-(2-Bromo-phenylmethanesulfonylamino)-pyrazine-2-carboxylic
acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 10.23 (bs, 1H),
8.59 (d, 1H), 8.43 (d, 1H), 7.52-7.60 (m, 2H), 7.33-7.36 (m, 1H),
7.22-7.27 (m, 1H), 5.13 (s, 2H), 4.03 (s, 3H) ppm.
[0287]
3-(2-Bromo-5-trifluoromethyl-phenylmethanesulfonylamino)-pyrazine-2-
-carboxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 10.31
(s, 1H), 8.59 (d, 1H), 8.47 (d, 1H), 7.74-7.76 (m, 2H), 7.48-7.51
(dd, 1H), 5.17 (s, 2H), 4.05 (s, 3H) ppm.
[0288]
3-(4-Bromo-2-trifluoromethyl-phenylmethanesulfonylamino)-pyrazine-2-
-carboxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 10.34
(s, 1H), 8.55 (d, 1H), 8.46 (d, 1H), 7.85 (s, 1H), 7.74 (d, 1H),
7.68 (d, 1H), 5.10 (s, 2H), 4.05 (s, 3H) ppm.
[0289]
3-(2-Chloro-3,6-difluoro-phenylmethanesulfonylamino)-pyrazine-2-car-
boxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 10.33 (bs,
1H), 8.60 (d, 1H), 8.46 (d, 1H), 7.17-7.23 (m, 1H), 7.00-7.06 (m,
1H), 5.18 (s, 2H), 4.05 (s, 3H) ppm.
[0290]
3-(2-Chloro-6-fluoro-3-methoxy-phenylmethanesulfonylamino)-pyrazine-
-2-carboxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3):
10.29 (bs, 1H), 8.60 (d, 1H), 8.44 (d, 1H), 6.92-7.03 (m, 2H), 5.19
(s, 2H), 4.03 (s, 3H), 3.88 (s, 3H) ppm.
[0291]
3-(2-Chloro-6-fluoro-5-methoxy-phenylmethanesulfonylamino)-pyrazine-
-2-carboxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3):
10.49 (bs, 1H), 8.56 (d, 1H), 8.48 (d, 1H), 7.34 (d, 1H), 7.19-7.22
(m, 1H), 7.03 (t, 1H), 4.08 (s, 3H), 3.91 (s, 3H) ppm.
[0292]
3-(2-Chloro-6-fluoro-3-methyl-phenyl)-methanesulfonylamino)-pyrazin-
e-2-carboxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3):
10.28 (s, 1H), 8.59 (d, 1H), 7.24-7.27 (m, 1H), 6.93 (t, 1H), 5.20
(s, 2H), 4.04 (s, 3H), 2.36 (s, 3H) ppm.
[0293]
3-(2-Chloro-4-iodo-phenylmethanesulfonylamino)-pyrazine-2-carboxyli-
c acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 10.23 (s, 1H),
8.57 (d, 1H), 8.45 (d, 1H), 7.76 (s, 1H), 7.63 (d, 1H), 7.24 (d,
1H), 5.03 (s, 2H), 4.04 (s, 3H) ppm.
[0294]
3-(2-Chloro-5-iodo-phenylmethanesulfonylamino)-pyrazine-2-carboxyli-
c acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 10.28 (s, 1H),
8.58 (d, 1H), 8.46 (d, 1H), 7.83 (d, 1H), 7.62-7.64 (dd, 1H), 7.13
(d, 1H), 5.03 (s, 2H), 4.05 (s, 3H) ppm.
[0295]
3-(2-Chloro-quinolin-3-yl)-methanesulfonylamino)-pyrazine-2-carboxy-
lic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 10.33 (s, 1H),
8.57 (d, 1H), 8.47 (d, 1H), 8.45 (s, 1H), 8.02 (d, 1H), 7.88 (d,
1H), 7.80 (dt, 1H), 7.62 (dt, 1H), 5.27 (s, 2H), 4.02 (s, 3H)
ppm.
[0296]
3-(2-Chloro-3-trifluoromethyl-phenylmethanesulfonylamino)-pyrazine--
2-carboxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 10.30
(s, 1H), 8.57 (d, 1H), 8.46 (d, 1H), 7.76 (t, 2H), 7.44 (t, 1H),
5.19 (s, 2H), 4.04 (s, 3H) ppm.
[0297]
3-(2-Chloro-6-trifluoromethyl-phenylmethanesulfonylamino)-pyrazine--
2-carboxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 10.38
(bs, 1H), 8.58 (d, 1H), 8.46 (d, 1H), 7.68-7.70 (d, 2H), 7.46-7.49
(m, 1H), 5.40 (s, 2H), 4.05 (s, 3H) ppm.
[0298]
3-(3-Chloro-5-trifluoromethyl-phenylmethanesulfonylamino)-pyrazine--
2-carboxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 10.24
(s, 1H), 8.61 (d, 1H), 8.50 (d, 1H), 7.64 (s, 1H), 7.60 (s, 1H),
7.50 (s, 1H), 4.92 (s, 2H), 4.04 (s, 3H) ppm.
[0299]
3-(4-Chloro-2-trifluoromethyl-phenylmethanesulfonylamino)-pyrazine--
2-carboxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 10.35
(bs, 1H), 8.56 (d, 1H), 8.46 (d, 1H), 7.71-7.77 (m, 2H), 7.57-7.60
(m, 1H), 5.12 (s, 2H), 4.05 (s, 3H) ppm.
[0300]
3-(5-Chloro-2-trifluoromethyl-phenylmethanesulfonylamino)-pyrazine--
2-carboxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 10.38
(s, 1H), 8.57 (d, 1H), 8.47 (d, 1H), 7.81 (s, 1H), 7.66 (d, 1H),
7.49 (d, 1H), 5.12 (s, 2H), 4.06 (s, 3H) ppm.
[0301] 3-(2-Cyano-phenylmethanesulfonylamino)-pyrazine-2-carboxylic
acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 10.24 (s, 1H),
8.63 (d, 1H), 8.47 (d, 1H), 7.64-7.72 (m, 3H), 7.50-7.53 (t, 1H),
5.15 (s, 2H), 4.04 (s, 3H) ppm.
[0302]
3-(2,6-Dibromo-phenylmethanesulfonylamino)-pyrazine-2-carboxylic
acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 10.39 (s, 1H),
8.57 (d, 1H), 8.43 (d, 1H), 7.60 (d, 2H), 7.07-7.11 (m, 1H), 5.42
(s, 2H), 4.05 (s, 3H) ppm.
[0303]
3-(2,3-Dichloro-6-fluoro-phenylmethanesulfonylamino)-pyrazine-2-car-
boxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 10.33 (bs,
1H), 8.59 (d, 1H), 8.45 (d, 1H), 7.48-7.52 (m, 1H), 7.00-7.05 (m,
1H), 5.21 (s, 2H), 4.05 (s, 3H) ppm.
[0304]
3-(2,4-Dichloro-5-fluoro-phenylmethanesulfonylamino)-pyrazine-2-car-
boxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 10.29 (s,
1H), 8.58 (d, 1H), 8.47 (d, 1H), 7.48 (d, 1H), 7.38 (d, 1H), 5.05
(s, 2H), 4.05 (s, 3H) ppm.
[0305]
3-(2,3-Dichloro-phenylmethanesulfonylamino)-pyrazine-2-carboxylic
acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 10.26 (s, 1H),
8.58 (d, 1H), 8.46 (d, 1H), 7.44-7.51 (m, 2H), 7.25 (t, 1H), 5.15
(s, 2H), 4.04 (s, 3H) ppm.
[0306]
3-(2,4-Dichloro-phenylmethanesulfonylamino)-pyrazine-2-carboxylic
acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 10.24 (bs, 1H),
8.58 (d, 1H), 8.46 (d, 1H), 7.46-7.48 (d, 1H), 7.42 (d, 1H),
7.28-7.31 (dd, 1H), 5.06 (s, 2H), 4.04 (s, 3H) ppm.
[0307]
3-(2,6-Dichloro-phenylmethanesulfonylamino)-pyrazine-2-carboxylic
acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 10.36 (bs, 1H),
8.58 (d, 1H), 8.43 (d, 1H), 7.37-7.39 (m, 2H), 7.25-7.29 (m, 1H),
5.34 (s, 2H), 4.05 (s, 3H) ppm.
[0308]
3-(3,4-Dichloro-phenylmethanesulfonylamino)-pyrazine-2-carboxylic
acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 10.17 (bs, 1H),
8.60 (d, 1H), 8.49 (d, 1H), 7.43-7.46 (m, 2H), 7.20-7.23 (m, 1H),
4.84 (s, 2H), 4.04 (s, 3H) ppm.
[0309]
3-(2,3-Dichloro-6-trifluoromethyl-phenylmethanesulfonylamino)-pyraz-
ine-2-carboxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3):
10.41 (s, 1H), 8.58 (d, 1H), 8.47 (d, 1H), 7.61-7.66 (m, 2H), 5.44
(s, 2H), 4.06 (s, 3H) ppm.
[0310]
3-(2,5-Dichloro-6-trifluoromethyl-phenylmethanesulfonylamino)-pyraz-
ine-2-carboxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3):
10.41 (s, 1H), 8.58 (d, 1H), 8.47 (d, 1H), 7.61-7.67 (m, 2H), 5.44
(s, 2H), 4.06 (s, 3H) ppm.
[0311]
3-(3-Ethoxycarbonyl-6-trifluoromethyl-pyrid-2-ylmethanesulfonylamin-
o)-pyrazine-2-carboxylic acid methyl ester. 1H-NMR (400 MHz,
CDCl.sub.3): 10.09 (s, 8.58 (d, 1H), 8.49 (d, 1H), 8.45 (d, 1H),
7.71 (d, 1H), 5.73 (s, 2H), 4.49 (q, 2H), 3.99 (s, 3H), 1.46 (t,
3H) ppm.
[0312]
3-(2-Fluoro-6-trifluoromethyl-phenylmethanesulfonylamino)-pyrazine--
2-carboxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 10.33
(s, 1H), 8.59 (d, 1H), 8.46 (d, 1H), 7.50-7.58 (m, 2H), 7.33 (t,
1H), 5.25 (s, 2H), 4.05 (s, 3H) ppm.
[0313] 3-(2-Iodo-phenylmethanesulfonylamino)-pyrazine-2-carboxylic
acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 10.24 (bs, 1H),
8.59 (d, 1H), 8.44 (d, 1H), 7.88 (d, 1H), 7.53 (dd, 1H), 7.37 (t,
1H), 7.06 (dt, 1H), 5.13 (s, 2H), 4.04 (s, 3H) ppm.
[0314]
3-(5-Methyl-2-trifluoromethyl-phenylmethanesulfonylamino)-pyrazine--
2-carboxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 10.32
(s, 1H), 8.57 (d, 1H), 8.45 (d, 1H), 7.60 (s, 1H), 7.58 (s, 1H),
7.29 (d, 1H), 5.11 (s, 2H), 4.05 (s, 3H), 2.43 (s, 3H) ppm.
[0315] 3-(2-Nitro-phenylmethanesulfonylamino)-pyrazine-2-carboxylic
acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 10.15 (s, 1H),
8.58 (d, 1H), 8.47 (d, 1H), 7.97 (d, 1H), 7.55-7.66 (m, 3H), 5.44
(s, 2H), 4.03 (s, 3H) ppm.
[0316]
3-(2,3,6-Trichloro-phenylmethanesulfonylamino)-pyrazine-2-carboxyli-
c acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 10.40 (bs, 1H),
8.57 (d, 1H), 8.45 (d, 1H), 7.45 (d, 1H), 7.33 (d, 1H), 5.38 (s,
2H), 4.05 (s, 3H) ppm.
[0317]
3-(2-Trifluoromethoxy-phenylmethanesulfonylamino)-pyrazine-2-carbox-
ylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 10.15 (bs,
1H), 8.59 (d, 1H), 8.45 (d, 1H), 7.58-7.61 (dd, 1H), 7.41-7.46 (m,
1H), 7.32-7.36 (m, 1H), 7.23-7.25 (m, 1H), 5.00 (s, 2H), 4.02 (s,
3H) ppm.
[0318]
3-(2-Trifluoromethyl-phenylmethanesulfonylamino)-pyrazine-2-carboxy-
lic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 10.31 (s, 1H),
8.57 (d, 1H), 8.45 (d, 1H), 7.80 (d, 1H), 7.72 (d, 1H), 7.61 (t,
1H), 7.51 (t, 1H), 5.16 (s, 2H), 4.05 (s, 3H) ppm.
[0319]
3-(3-Trifluoromethyl-phenylmethanesulfonylamino)-pyrazine-2-carboxy-
lic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 10.16 (bs,
1H), 8.61 (d, 1H), 8.48 (d, 1H), 7.49-7.66 (m, 4H), 4.95 (s, 2H),
4.03 (s, 3H) ppm.
[0320]
3-(2-Trifluoromethylthio-phenylmethanesulfonylamino)-pyrazine-2-car-
boxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 10.21 (bs,
1H), 8.62 (d, 1H), 8.48 (d, 1H), 7.81-7.83 (dd, 1H), 7.58-7.60 (m,
1H), 7.45-7.54 (m, 2H), 5.31 (s, 2H), 4.04 (s, 3H) ppm.
Example 2.2
Preparation of
3-[(2-chloro-3,6-difluoro-phenylmethanesulfonyl)-methyl-amino]-pyrazine-2-
-carboxylic acid methyl ester
##STR00029##
[0322] To a solution of
3-(2-chloro-3,6-difluoro-phenylmethanesulfonylamino)-pyrazine-2-carboxyli-
c acid methyl ester (Example 2.1) (420 mg) in acetonitrile (4 ml)
was added N,N-diisopropylethylamine ("Hunig's base") (0.39 ml) and
methyl iodide (0.28 ml). The reaction mixture was heated in a
microwave at 150.degree. C. for 30 minutes. The reaction mixture
was allowed to cool to ambient temperature and then partitioned
between diethyl ether and aqueous hydrochloric acid (2M). The
phases were separated. The aqueous layer was extracted with diethyl
ether. The combined organic extracts were washed with brine and
concentrated to give
3-[(2-chloro-3,6-difluoro-phenylmethane-sulfonyl)-methyl-amino]-pyrazine--
2-carboxylic acid methyl ester as an orange oil (0.307 g). 1H-NMR
(400 MHz, CDCl.sub.3): 8.58 (d, 1H), 8.56 (d, 1H), 7.13-7.19 (m,
1H), 7.00-7.06 (m, 1H), 4.82 (s, 2H), 4.02 (s, 3H), 3.51 (s, 3H)
ppm.
[0323] The following compound was made using the same method:
[0324]
3-[(2-Chloro-quinolin-3-ylmethanesulfonyl)-methyl-amino]-pyrazine-2-
-carboxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 8.54
(d, 1H), 8.53 (d, 1H), 8.45 (s, 1H), 8.10 (d, 1H), 7.92 (d, 1H),
7.84 (dt, 1H), 7.65 (dt, 1H), 4.88 (s, 2H), 4.02 (s, 3H), 3.53 (s,
3H) ppm.
[0325]
3-[(2-Chloro-5-trifluoromethyl-phenylmethanesulfonyl)-methyl-amino]-
-pyrazine-2-carboxylic acid methyl ester. 1H-NMR (400 MHz,
CDCl.sub.3): 8.58 (d, 1H), 8.53 (d, 1H), 7.83 (bs, 1H), 7.54-7.56
(m, 2H), 4.76 (s, 2H), 4.03 (s, 3H), 3.43 (s, 3H) ppm.
[0326]
3-[(2,4-Dichloro-phenylmethanesulfonyl)-methyl-amino]-pyrazine-2-ca-
rboxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 8.55 (d,
1H), 8.48 (d, 1H), 7.44-7.46 (m, 2H), 7.16-7.18 (m, 1H), 4.67 (s,
2H), 4.02 (s, 3H), 3.43 (s, 3H) ppm.
[0327]
3-[(2,3,6-Trichloro-phenylmethanesulfonyl)-methyl-amino]-pyrazine-2-
-carboxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 8.61
(d, 1H), 8.59 (d, 1H), 7.41 (d, 1H), 7.31 (d, 1H), 5.03 (s, 2H),
4.02 (s, 3H), 3.54 (s, 3H) ppm.
Example 23
Preparation of
3-[(2-chloro-5-trifluoromethyl-phenylmethanesulfonyl)-ethyl-amino]-pyrazi-
ne-2-carboxylic acid methyl ester
##STR00030##
[0329] To a solution of
3-(2-chloro-5-trifluoromethyl-phenylmethanesulfonylamino)-pyrazine-2-carb-
oxylic acid methyl ester (Example 2.1) (1.5 g) in acetonitrile (20
ml) was added N,N-diisopropylethylamine ("Hunig's base") (0.71 ml)
at ambient temperature. The mixture was stirred for 5 minutes at
ambient temperature before dropwise addition of a solution of
ethyltrifluoromethanesulfonate (0.71 ml) in acetonitrile (5 ml) at
ambient to temperature. The reaction mixture was stirred at ambient
temperature for 4 hours. The reaction mixture was concentrated and
the residue purified by column chromatography on silica gel
(eluent: dichloromethane) to give
3-[(2-chloro-5-trifluoromethyl-phenyl-methanesulfonyl)-ethyl-amino]-pyraz-
ine-2-carboxylic acid methyl ester as a beige solid (0.968 g).
1H-NMR (400 MHz, CDCl.sub.3): 8.57 (d, 1H), 8.52 (d, 1H), 7.77 (m,
1H), 7.50-7.56 (m, 2H), 4.64 (m, 2H), 4.01 (q, 2H), 4.00 (s, 3H),
1.23 (t, 3H) ppm.
[0330] The following compounds were made using the same method:
[0331]
3-[(2,5-Bis-(trifluoromethyl)-phenylmethanesulfonyl)-ethyl-amino]-p-
yrazine-2-carboxylic acid methyl ester. 1H-NMR (400 MHz,
CDCl.sub.3): 8.66 (d, 1H), 8.58 (d, 1H), 7.96 (s, 1H), 7.84 (d,
1H), 7.71 (d, 1H), 4.62 (s, 2H), 4.04 (q, 2H), 4.01 (s, 3H), 1.26
(t, 3H) ppm.
[0332]
3-[(3-Bromo-2-chloro-6-fluoro-phenylmethanesulfonyl)-ethyl-amino]-p-
yrazine-2-carboxylic acid methyl ester. 1H-NMR (400 MHz,
CDCl.sub.3): 8.59-8.61 (m, 2H), 7.57-7.64 (m, 1H), 6.92-6.99 (m,
1H), 4.74 (s, 2H), 4.10-4.15 (q, 2H), 4.03 (s, 3H), 1.29 (t, 3H)
ppm.
[0333]
3-[(2-Bromo-5-trifluoromethyl-phenylmethanesulfonyl)-ethyl-amino]-p-
yrazine-2-carboxylic acid methyl ester. 1H-NMR (400 MHz,
CDCl.sub.3): 8.59 (d, 1H), 8.54 (d, 1H), 7.73-7.77 (m, 2H),
7.42-7.44 (dd, 1H), 4.66 (s, 2H), 4.03 (q, 2H), 4.01 (s, 3H), 1.26
(t, 3H) ppm.
[0334]
3-[(2-Chloro-6-fluoro-3-methoxy-phenylmethanesulfonyl)-ethyl-amino]-
-pyrazine-2-carboxylic acid methyl ester. 1H-NMR (400 MHz,
CDCl.sub.3): 8.57-8.59 (m, 2H), 6.96-7.01 (m, 1H), 6.86-6.89 (m,
1H), 4.70 (s, 2H), 4.11 (q, 2H), 3.99 (s, 3H), 3.86 (s, 3H), 1.27
(t, 3H) ppm.
[0335]
3-[(2-Chloro-6-fluoro-3-methyl-phenylmethanesulfonyl)-ethyl-amino]--
pyrazine-2-carboxylic acid methyl ester. 1H-NMR (400 MHz,
CDCl.sub.3): 10.28 (bs, 1H), 8.59 (d, 1H), 8.44 (d, 1H), 7.24-7.27
(m, 1H), 6.91-6.95 (m, 1H), 5.20 (s, 2H), 4.04 (s, 3H), 2.36 (s,
3H) ppm.
[0336]
3-[(2,4-Dichloro-5-fluoro-phenylmethanesulfonyl)-ethyl-amino]-pyraz-
ine-2-carboxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3):
8.41-8.44 (m, 2H), 7.30 (d, 1H), 7.15 (d, 1H), 4.26 (q, 2H), 3.85
(q, 2H), 3.79 (s, 3H), 1.23 (t, 3H) ppm.
[0337]
3-[(3,4-Dichloro-phenylmethanesulfonyl)-ethyl-amino]-pyrazine-2-car-
boxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 8.58 (d,
1H), 8.55 (d, 1H), 7.52-7.53 (m, 1H), 7.39-7.41 (m, 1H), 7.24-7.26
(m, 1H), 4.27 (s, 2H), 4.01 (s, 3H), 3.86 (q, 2H), 1.15 (t, 3H)
ppm.
[0338]
3-[(2-Fluoro-6-trifluoromethyl-phenylmethanesulfonyl)-ethyl-amino]--
pyrazine-2-carboxylic acid methyl ester. 1H-NMR (400 MHz,
CDCl.sub.3): 8.65 (d, 1H), 8.63 (d, 1H), 7.43-7.50 (m, 2H),
7.27-7.31 (m, 1H), 4.70-4.71 (m, 2H), 4.46 (q, 2H), 3.99 (s, 3H),
1.28 (t, 3H) ppm.
[0339]
3-[(2-Trifluoromethyl-phenylmethanesulfonyl)-ethyl-amino]-pyrazine--
2-carboxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 8.62
(d, 1H), 8.61 (d, 1H), 7.65-7.69 (m, 2H), 7.42-7.51 (m, 2H), 4.58
(s, 2H), 4.06 (q, 2H), 3.99 (s, 3H), 1.26 (t, 3H), ppm.
[0340]
3-[(2-Trifluoromethylthio-phenylmethanesulfonyl)-ethyl-amino]-pyraz-
ine-2-carboxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3):
8.56 (d, 1H), 8.53 (d, 1H), 7.75-7.77 (m, 1H), 7.57-7.59 (m, 1H),
7.36-7.46 (m, 2H), 4.74 (s, 2H), 4.01 (q, 2H), 3.99 (s, 3H), 1.23
(t, 3H) ppm.
Example 2.4
Preparation of
3-[(2,3-dichloro-6-fluoro-phenylmethanesulfonyl)-ethyl-amino]-pyrazine-2--
carboxylic acid ethyl ester
##STR00031##
[0342] To a solution of
3-(2,3-dichloro-6-fluoro-phenylmethanesulfonylamino)-pyrazine-2-carboxyli-
c acid methyl ester (Example 2.1) (250 mg) in
N,N-dimethyl-formamide (2 ml) was added N,N-diisopropylethylamine
("Hunig's base") (0.22 ml) and ethyl iodide (0.152 ml). The
reaction mixture was heated in a microwave at 150.degree. C. for 30
minutes. The reaction mixture was allowed to cool to ambient
temperature and concentrated. The residue was purified by column
chromatography on silica gel (eluent: ethyl acetate/dichloromethane
1:9) to give
3-[(2,3-dichloro-6-fluoro-phenylmethane-sulfonyl)-ethyl-amino]-pyrazine-2-
-carboxylic acid ethyl ester as a beige solid (0.206 g). 1H-NMR
(400 MHz, CDCl.sub.3): 8.62 (d, 1H), 8.58 (d, 1H), 7.41-7.44 (m,
1H), 6.97-7.01 (m, 1H), 4.70 (m, 2H), 4.47 (q, 2H), 4.10 (q, 3H),
1.43 (t, 3H), 1.27 (t, 3H) ppm.
[0343] In this example, N-alkylation was accompanied by
transesterification (that is, the starting material was a methyl
ester and the product isolated was identified as an ethyl ester).
In the analogous reactions listed below, transesterification was
during the N-alkylation was observed only in one further case.
[0344] The following compounds were made using the same method:
[0345]
3-[(2,6-Bis-(trifluoromethyl)-phenylmethanesulfonyl)-ethyl-amino]-p-
yrazine-2-carboxylic acid methyl ester. 1H-NMR (400 MHz,
CDCl.sub.3): 8.66 (m, 2H), 7.88 (d, 2H), 7.59 (t, 1H), 4.89 (s,
2H), 4.10 (q, 2H), 3.95 (s, 3H), 1.27 (t, 3H) ppm.
[0346]
3-[(2-Chloro-6-trifluoromethyl-phenylmethanesulfonyl)-ethyl-amino]--
pyrazine-2-carboxylic acid methyl ester. The crude compound was
used directly for further synthesis.
[0347]
3-[(2-Trifluoromethoxy-phenylmethanesulfonyl)-ethyl-amino]-pyrazine-
-2-carboxylic acid methyl ester. The crude compound was used
directly for further synthesis.
[0348]
3-[(2-Chloro-5-iodo-phenylmethanesulfonyl)-ethyl-amino]-pyrazine-2--
carboxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 8.58
(d, 1H), 8.55 (d, 1H), 7.77 (d, 1H), 7.54-7.57 (dd, 1H), 7.13 (d,
1H), 4.52 (s, 2H), 4.02 (q, 2H), 4.00 (s, 3H), 1.22-1.25 (m, 3H)
ppm.
[0349]
3-[(2-Chloro-3-trifluoromethyl-phenylmethanesulfonyl)-ethyl-amino]--
pyrazine-2-carboxylic acid methyl ester. 1H-NMR (400 MHz,
CDCl.sub.3): 8.52 (d, 1H), 8.46 (d, 1H), 7.66 (d, 2H), 7.26 (t,
1H), 4.69 (s, 2H), 4.08 (q, 2H), 3.99 (s, 3H), 1.26 (t, 3H)
ppm.
[0350]
3-[(4-Chloro-2-trifluoromethyl-phenylmethanesulfonyl)-ethyl-amino]--
pyrazine-2-carboxylic acid methyl ester. 1H-NMR (400 MHz,
CDCl.sub.3): 8.62 (d, 1H), 8.56 (d, 1H), 7.67 (d, 1H), 7.59-7.61
(d, 1H), 7.42-7.44 (dd, 1H), 4.52 (s, 2H), 4.04 (q, 2H), 4.00 (s,
3H), 1.25 (t, 3H) ppm.
[0351]
3-[(5-Chloro-2-trifluoromethyl-phenylmethanesulfonyl)-ethyl-amino]--
pyrazine-2-carboxylic acid methyl ester. 1H-NMR (400 MHz,
CDCl.sub.3): 8.63 (d, 1H), 8.59 (d, 1H), 7.67 (s, 1H), 7.62 (d,
1H), 7.41 (d, 1H), 4.53 (s, 2H), 4.04 (q, 2H), 4.01 (s, 3H), 1.26
(t, 3H) ppm.
[0352]
3-[(3-Trifluoromethyl-phenylmethanesulfonyl)-ethyl-amino]-pyrazine--
2-carboxylic acid ethyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 8.57
(d, 1H), 8.51 (d, 1H), 7.70 (m, 1H), 7.59-7.62 (m, 2H), 7.43-7.47
(m, 1H), 4.46 (q, 2H), 4.38 (s, 2H), 3.85 (q, 2H), 1.44 (t, 3H),
1.13 (t, 3H) ppm.
[0353]
3-[(2,3-Dichloro-phenylmethanesulfonyl)-ethyl-amino]-pyrazine-2-car-
boxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 8.53 (d,
1H), 8.49 (d, 1H), 7.36-7.42 (m, 2H), 7.09 (t, 1H), 4.63 (s, 2H),
4.06 (q, 2H), 3.99 (s, 3H), 1.23 (t, 3H) ppm.
[0354]
3-[(2,4-Dichloro-phenylmethanesulfonyl)-ethyl-amino]-pyrazine-2-car-
boxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 8.55 (d,
1H), 8.47 (d, 1H), 7.43 (d, 1H), 7.37-7.39 (d, 1H), 7.12-7.44 (d,
1H), 4.54 (s, 2H), 4.03-4.06 (q, 2H), 4.00 (s, 3H), 1.25 (t, 3H)
ppm.
[0355]
3-[(2,5-Dichloro-6-trifluoromethyl-phenylmethanesulfonyl)-ethyl-ami-
no]-pyrazine-2-carboxylic acid methyl ester. 1H-NMR (400 MHz,
CDCl.sub.3): 8.66-8.67 (m, 2H), 7.53-7.59 (m, 2H), 4.91 (s, 2H),
4.14 (q, 2H), 3.99 (s, 3H), 1.29 (t, 3H) ppm.
[0356]
3-[(2-Nitro-phenylmethanesulfonyl)-ethyl-amino]-pyrazine-2-carboxyl-
ic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 8.60 (d, 1H),
8.58 (d, 1H), 8.05 (d, 1H), 7.49-7.58 (m, 3H), 4.96 (s, 2H), 3.98
(s, 3H), 3.94 (q, 2H), 1.18 (t, 3H) ppm.
[0357]
3-[(2,3,6-Trichloro-phenylmethanesulfonyl)-ethyl-amino]pyrazine-2-c-
arboxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3):
8.63-8.64 (m, 2H), 7.39 (d, 1H), 7.28 (d, 1H), 4.88 (s, 2H), 4.14
(q, 2H), 4.00 (s, 3H), 1.29 (t, 3H) ppm.
Example 2.5
Preparation of
3-[(2-trifluoromethylthio-phenylmethanesulfonyl)-methoxy-methyl-amino]-py-
razine-2-carboxylic acid methyl ester
##STR00032##
[0359] To a solution of
3-(2-trifluoromethylthio-phenylmethanesulfonylamino)-pyrazine-2-carboxyli-
c acid methyl ester (Example 2.1) (250 mg) in acetonitrile (5 ml)
was added N,N-diisopropylethylamine ("Hunig's base") (0.12 ml) at
ambient temperature. The mixture was stirred for 5 minutes at
ambient temperature before addition of the iodomethylmethyl ether
(0.105 ml). The reaction mixture was stirred at ambient temperature
for 18 hours. The reaction mixture was concentrated. The residue
was purified by column chromatography on silica gel (eluent: ethyl
acetate/dichloromethane 5:95) to give
3-[(2-trifluoromethylthio-phenylmethanesulfonyl)-methoxymethyl-am-
ino]-pyrazine-2-carboxylic acid methyl ester as a dark orange gum
(0.221 g). 1H-NMR (400 MHz, CDCl.sub.3): 8.66 (d, 1H), 8.64 (d,
1H), 7.78-7.80 (m, 1H), 7.63-7.66 (m, 1H), 7.41-7.51 (m, 2H), 5.18
(s, 2H), 4.98 (s, 2H), 4.01 (s, 3H), 3.51 (s, 3H) ppm.
[0360] The following compound was made using the same method:
[0361]
3-[(2,4-Dichloro-phenylmethanesulfonyl)-methoxymethyl-amino]-pyrazi-
ne-2-carboxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3):
8.60 (d, 1H), 7.78-7.80 (m, 1H), 7.45-7.47 (m, 2H), 7.19-7.22 (dd,
1H), 5.23 (s, 2H), 4.78 (s, 2H), 4.01 (s, 3H), 3.51 (s, 3H)
ppm.
Example 2.6
Preparation of
3-[(2-chloro-5-trifluoromethyl-phenylmethanesulfonyl)-(2,2-difluoro-ethyl-
)-amino]-pyrazine-2-carboxylic acid methyl ester
##STR00033##
[0363] To a solution of
3-(2-chloro-5-trifluoromethyl-phenylmethanesulfonylamino)-pyrazine-2-carb-
oxylic acid methyl ester (Example 2.1) (1.5 g) in acetonitrile (15
ml) was added N,N-diisopropylethylamine ("Hunig's base") (0.71 ml)
at ambient temperature. The mixture was stirred for 5 minutes at
ambient temperature before dropwise addition of a solution of
2,2-difluoroethyltrifluoromethanesulfonate (1.2 g) in acetonitrile
(5 ml) at ambient temperature. The reaction mixture was stirred at
ambient temperature for 44 hours. The reaction mixture was
concentrated. The residue was purified by column chromatography on
silica gel (eluent: dichloromethane) to give
3-[(2-chloro-5-trifluoro-methyl-phenylmethanesulfonyl)-(2,2-difluoro-ethy-
l)-amino]-pyrazine-2-carboxylic acid methyl ester as a light yellow
solid (1.300 g). 1H-NMR (400 MHz, CDCl.sub.3): 8.63 (s, 1H), 8.53
(s, 1H), 7.76 (m, 1H), 7.53-7.59 (m, 2H), 6.15 (tt, 1H), 4.69 (s,
2H), 4.23-4.31 (m, 2H), 4.02 (s, 3H) ppm.
[0364] The following compounds were made using the same method:
[0365]
3-[(2,4-Bis-(trifluoromethyl)-phenylmethanesulfonyl)-(2,2-difluoro--
ethyl)-amino]-pyrazine-2-carboxylic acid methyl ester. 1H-NMR (400
MHz, CDCl.sub.3): 8.66 (d, 1H), 8.52 (d, 1H), 7.95 (s, 1H), 7.80
(d, 1H), 7.72 (d, 1H), 6.01-6.31 (tt, 1H), 4.70 (s, 2H), 4.29-4.36
(dt, 2H), 4.01 (s, 3H) ppm.
[0366]
3-[(2,5-Bis-(trifluoromethyl)-phenylmethanesulfonyl)-(2,2-difluoro--
ethyl)-amino]-pyrazine-2-carboxylic acid methyl ester. 1H-NMR (400
MHz, CDCl.sub.3): 8.69 (d, 1H), 8.58 (d, 1H), 7.94 (s, 1H), 7.86
(d, 1H), 7.73 (d, 1H), 6.02-6.32 (tt, 1H), 4.71 (s, 2H), 4.27-4.34
(dt, 2H), 4.02 (s, 3H) ppm.
[0367]
3-[(2,6-Bis-(trifluoromethyl)-phenylmethanesulfonyl)-(2,2-difluoro--
ethyl)-amino]-pyrazine-2-carboxylic acid methyl ester. 1H-NMR (400
MHz, CDCl.sub.3): 8.73 (d, 1H), 8.69 (d, 1H), 7.91 (d, 2H), 7.63
(t, 1H), 6.04-6.34 (tt, 1H), 5.00 (s, 2H), 4.36-4.43 (dt, 2H), 3.99
(s, 3H) ppm.
[0368]
3-[(3-Bromo-2-chloro-6-fluoro-phenylmethanesulfonyl)-(2,2-difluoro--
ethyl)-amino]-pyrazine-2-carboxylic acid methyl ester. 1H-NMR (400
MHz, CDCl.sub.3): 8.64 (d, 1H), 8.57 (d, 1H), 7.59-7.63 (m, 1H),
6.92-6.97 (m, 1H), 6.05-6.33 (tt, 1H), 4.80 (s, 2H), 4.34-4.42 (m,
2H), 4.01 (s, 3H) ppm.
[0369]
3-[(2-Bromo-phenylmethanesulfonyl)-(2,2-difluoro-ethyl)-amino]pyraz-
ine-2-carboxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3):
8.58 (d, 1H), 8.48 (d, 1H), 7.45-7.63 (m, 2H), 7.17-7.23 (m, 2H),
5.98-6.28 (tt, 1H), 4.65 (s, 2H), 4.26-4.34 (m, 2H), 4.01 (s, 3H)
ppm.
[0370]
3-[(2-Bromo-5-trifluoromethyl-phenylmethanesulfonyl)-(2,2-difluoro--
ethyl)-amino]-pyrazine-2-carboxylic acid methyl ester. 1H-NMR (400
MHz, CDCl.sub.3): 8.64 (d, 1H), 8.55 (d, 1H), 7.75-7.77 (m, 2H),
7.45-7.47 (m, 1H), 6.00-6.30 (tt, 1H), 4.71 (s, 2H), 4.24-4.32 (dt,
2H), 4.02 (s, 3H) ppm.
[0371]
3-[(4-Bromo-2-trifluoromethyl-phenylmethanesulfonyl)-(2,2-difluoro--
ethyl)-amino]-pyrazine-2-carboxylic acid methyl ester. 1H-NMR (400
MHz, CDCl.sub.3): 8.66 (d, 1H), 8.53 (d, 1H), 7.83 (d, 1H),
7.57-7.60 (dd, 1H), 7.49 (d, 1H), 6.00-6.30 (tt, 1H), 4.57 (s, 2H),
4.26-4.34 (dt, 2H), 4.01 (s, 3H) ppm.
[0372]
3-[(2-Chloro-6-fluoro-3-methoxy-phenylmethanesulfonyl)-(2,2-difluor-
o-ethyl)-amino]-pyrazine-2-carboxylic acid methyl ester. 1H-NMR
(400 MHz, CDCl.sub.3): 8.63 (d, 1H), 8.57 (d, 1H), 6.98-7.03 (m,
1H), 6.88-6.91 (m, 1H), 6.03-6.33 (tt, 1H), 4.75 (s, 2H), 4.35-4.42
(m, 2H), 4.00 (s, 3H), 3.87 (s, 3H) ppm.
[0373]
3-[(2-Chloro-6-fluoro-5-methoxy-phenylmethanesulfonyl)-(2,2-difluor-
o-ethyl)-amino]-pyrazine-2-carboxylic acid methyl ester. 1H-NMR
(400 MHz, CDCl.sub.3): 8.62 (d, 1H), 8.55 (d, 1H), 7.13 (d, 1H),
6.90 (t, 1H), 6.03-6.32 (m, 1H), 4.71 (s, 2H), 4.35-4.42 (dt, 2H),
4.00 (s, 3H), 3.88 (s, 3H) ppm.
[0374]
3-[(2-Chloro-6-fluoro-3-methyl-phenylmethanesulfonyl)-(2,2-difluoro-
-ethyl)-amino]pyrazine-2-carboxylic acid methyl ester. 1H-NMR (400
MHz, CDCl.sub.3): 8.62 (d, 1H), 8.55 (d, 1H), 7.19-7.22 (m, 1H),
6.91-6.96 (m, 1H), 6.03-6.33 (tt, 1H), 4.75 (s, 2H), 4.35-4.42 (m,
2H), 4.00 (s, 3H), 2.34 (s, 3H) ppm.
[0375]
3-[(2-Chloro-4-iodo-phenylmethanesulfonyl)-(2,2-difluoro-ethyl)-ami-
no]-pyrazine-2-carboxylic acid methyl ester. 1H-NMR (400 MHz,
CDCl.sub.3): 8.60 (d, 1H), 8.47 (d, 1H), 7.80 (s, 1H), 7.48 (d,
1H), 7.13 (d, 1H), 5.98-6.28 (tt, 1H), 4.57 (s, 2H), 4.25-4.32 (dt,
2H), 4.00 (s, 3H) ppm.
[0376]
3-[(2-Chloro-5-iodo-phenylmethanesulfonyl)-(2,2-difluoro-ethyl)-ami-
no]-pyrazine-2-carboxylic acid methyl ester. 1H-NMR (400 MHz,
CDCl.sub.3): 8.64 (d, 1H), 8.55 (d, 1H), 7.77 (d, 1H), 7.58-7.60
(dd, 1H), 7.16 (d, 1H), 6.00-6.30 (tt, 1H), 4.56 (s, 2H), 4.24-4.32
(m, 2H), 4.02 (s, 3H) ppm.
[0377]
3-[(2-Chloro-3-trifluoromethyl-phenylmethanesulfonyl)-(2,2-difluoro-
-ethyl)-amino]-pyrazine-2-carboxylic acid methyl ester. 1H-NMR (400
MHz, CDCl.sub.3): 8.56 (d, 1H), 8.42 (d, 1H), 7.62-7.68 (m, 2H),
7.26 (t, 1H), 6.00-6.30 (tt, 1H), 4.73 (s, 2H), 4.29-4.37 (dt, 2H),
4.00 (s, 3H) ppm.
[0378]
3-[(2-Chloro-6-trifluoromethyl-phenylmethanesulfonyl)-(2,2-difluoro-
-ethyl)-amino]-pyrazine-2-carboxylic acid methyl ester. 1H-NMR (400
MHz, CDCl.sub.3): 8.71 (d, 1H), 8.66 (d, 1H), 7.62-7.64 (m, 2H),
7.41-7.44 (m, 1H), 6.07-6.31 (tt, 1H), 4.94 (s, 2H), 4.40-4.46 (m,
2H), 4.00 (s, 3H) ppm.
[0379]
3-[(3-Chloro-5-trifluoromethyl-phenylmethanesulfonyl)-(2,2-difluoro-
-ethyl)-amino]-pyrazine-2-carboxylic acid methyl ester. 1H-NMR (400
MHz, CDCl.sub.3): 8.67 (d, 1H), 8.59 (d, 1H), 7.62 (s, 2H), 7.60
(s, 1H), 5.93-6.23 (tt, 1H), 4.41 (s, 2H), 4.09-4.17 (dt, 2H), 4.02
(s, 3H) ppm.
[0380]
3-[(5-Chloro-2-trifluoromethyl-phenylmethanesulfonyl)-(2,2-difluoro-
-ethyl)-amino]-pyrazine-2-carboxylic acid methyl ester. 1H-NMR (400
MHz, CDCl.sub.3): 8.68 (d, 1H), 8.58 (d, 1H), 7.64 (s, 1H), 7.63
(d, 1H), 7.43 (d, 1H), 6.02-6.31 (tt, 1H), 4.60 (s, 2H), 4.27-4.35
(dt, 2H), 4.02 (s, 3H) ppm.
[0381]
3-[(2-Cyano-phenylmethanesulfonyl)-(2,2-difluoro-ethyl)-amino]-pyra-
zine-2-carboxylic acid methyl ester. 1H-NMR (400 MHz,
d.sub.6-DMSO): 8.72 (d, 1H), 8.70 (d, 1H), 7.80 (d, 1H), 7.62-7.66
(m, 1H), 7.55-7.57 (m, 1H), 7.49 (t, 1H), 6.05-6.35 (tt, 1H), 4.84
(s, 2H), 4.30-4.38 (dt, 2H), 3.78 (s, 3H) ppm.
[0382]
3-[(2,6-Dibromo-phenylmethanesulfonyl)-(2,2-difluoro-ethyl)-amino]--
pyrazine-2-carboxylic acid methyl ester. 1H-NMR (400 MHz,
CDCl.sub.3): 8.64-8.68 (m, 2H), 7.54-7.56 (m, 2H), 7.02-7.06 (m,
1H), 6.06-6.34 (m, 1H), 4.96 (s, 2H), 4.42-4.48 (m, 2H), 4.00 (s,
3H) ppm.
[0383]
3-[(2,3-Dichloro-6-fluoro-phenylmethanesulfonyl)-(2,2-difluoro-ethy-
l)-amino]-pyrazine-2-carboxylic acid methyl ester. 1H-NMR (400 MHz,
CDCl.sub.3): 8.65 (d, 1H), 8.57 (d, 1H), 7.43-7.47 (m, 1H),
6.99-7.03 (m, 1H), 6.04-6.33 (tt, 1H), 4.78 (s, 2H), 4.35-4.42 (m,
2H), 4.01 (s, 3H) ppm.
[0384]
3-[(2,4-Dichloro-5-fluoro-phenylmethanesulfonyl)-(2,2-difluoro-ethy-
l)-amino]-pyrazine-2-carboxylic acid methyl ester. 1H-NMR (400 MHz,
CDCl.sub.3): 8.66 (d, 1H), 8.55 (d, 1H), 7.44 (d, 1H), 7.33 (d,
1H), 6.00-6.30 (tt, 1H), 4.58 (s, 2H), 4.25-4.33 (dt, 2H), 4.01 (s,
3H) ppm.
[0385]
3-[(2,3-Dichloro-phenylmethanesulfonyl)-(2,2-difluoro-ethyl)-amino]-
-pyrazine-2-carboxylic acid methyl ester. 1H-NMR (400 MHz,
CDCl.sub.3): 8.57 (d, 1H), 8.48 (d, 1H), 7.44 (d, 1H), 7.36 (d,
1H), 7.10 (t, 1H), 5.99-6.29 (tt, 1H), 4.68 (s, 2H), 4.27-4.34 (dt,
2H), 4.01 (s, 3H) ppm.
[0386]
3-[(2,6-Dichloro-phenylmethanesulfonyl)-(2,2-difluoro-ethyl)-amino]-
-pyrazine-2-carboxylic acid methyl ester. 1H-NMR (400 MHz,
CDCl.sub.3): 8.67 (d, 1H), 8.62 (d, 1H), 7.33-7.35 (m, 2H),
7.21-7.27 (m, 1H), 6.04-6.34 (tt, 1H), 4.90 (s, 2H), 4.38-4.46 (m,
2H), 4.00 (s, 3H) ppm.
[0387]
3-[(2,3-Dichloro-6-trifluoromethyl-phenylmethanesulfonyl)-(2,2-difl-
uoro-ethyl)-amino]-pyrazine-2-carboxylic acid methyl ester. 1H-NMR
(400 MHz, CDCl.sub.3): 8.72 (d, 1H), 8.67 (d, 1H), 7.55-7.61 (m,
2H), 6.07-6.31 (tt, 1H), 4.99 (s, 2H), 4.39-4.45 (dt, 2H), 4.00 (s,
3H) ppm.
[0388]
3-[(2,5-Dichloro-6-trifluoromethyl-phenylmethanesulfonyl)-(2,2-difl-
uoro-ethyl)-amino]-pyrazine-2-carboxylic acid methyl ester. 1H-NMR
(400 MHz, CDCl.sub.3): 8.72 (d, 1H), 8.67 (d, 1H), 7.55-7.61 (m,
2H), 6.05-6.34 (tt, 1H), 4.99 (s, 2H), 4.38-4.46 (dt, 2H), 4.00 (s,
3H) ppm.
[0389]
3-[(3-Ethoxycarbonyl-6-trifluoromethyl-pyrid-2-ylmethanesulfonyl)-(-
2,2-difluoro-ethyl)-amino]-pyrazine-2-carboxylic acid methyl ester.
1H-NMR (400 MHz, CDCl.sub.3): 8.59 (d, 1H), 8.50 (d, 1H), 8.35 (d,
1H), 7.73 (d, 2H), 6.04-6.28 (tt, 1H), 5.33 (s, 2H), 4.36 (q, 2H),
4.28-4.34 (dt, 2H), 3.98 (s, 3H), 1.37 (t, 3H) ppm.
[0390]
3-[(2-Fluoro-6-trifluoromethyl-phenylmethanesulfonyl)-(2,2-difluoro-
-ethyl)-amino]-pyrazine-2-carboxylic acid methyl ester. 1H-NMR (400
MHz, CDCl.sub.3): 8.68 (s, 1H), 8.64 (s, 1H), 7.45-7.51 (m, 2H),
7.30-7.34 (t, 1H), 6.03-6.33 (tt, 1H), 4.79 (s, 2H), 4.36-4.44 (dt,
2H), 4.00 (s, 3H) ppm.
[0391]
3-[(2-Iodo-phenylmethanesulfonyl)-(2,2-difluoro-ethyl)-amino]pyrazi-
ne-2-carboxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3):
8.61 (d, 1H), 8.53 (d, 1H), 7.88 (d, 1H), 7.48 (dd, 1H), 7.27 (t,
1H), 7.01 (dt, 1H), 6.00-6.29 (tt, 1H), 4.63 (s, 2H), 4.32 (dt,
2H), 4.01 (s, 3H) ppm.
[0392]
3-[(5-Methyl-2-trifluoromethyl-phenylmethanesulfonyl)-(2,2-difluoro-
-ethyl)-amino]-pyrazine-2-carboxylic acid methyl ester. 1H-NMR (400
MHz, CDCl.sub.3): 8.63 (d, 1H), 8.53 (d, 1H), 7.57 (d, 1H), 7.41
(s, 1H), 7.23 (d, 1H), 6.00-6.30 (tt, 1H), 4.57 (s, 2H), 4.27-4.35
(dt, 2H), 4.01 (s, 3H), 2.33 (s, 3H) ppm.
[0393]
3-[(2-Nitro-phenylmethanesulfonyl)-(2,2-difluoro-ethyl)-amino]-pyra-
zine-2-carboxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3):
8.64 (d, 1H), 8.57 (d, 1H), 8.09 (d, 1H), 7.52-7.62 (m, 3H),
5.94-6.24 (m, 1H), 5.02 (s, 2H), 4.16-4.24 (dt, 2H), 3.98 to (s,
3H) ppm.
[0394]
3-[(2,3,6-Trichloro-phenylmethanesulfonyl)-(2,2-difluoro-ethyl)-ami-
no]-pyrazine-2-carboxylic acid methyl ester. 1H-NMR (400 MHz,
CDCl.sub.3): 8.69 (d, 1H), 8.63 (d, 1H), 7.41 (d, 1H), 7.29 (d,
1H), 6.04-6.34 (tt, 1H), 4.95 (s, 2H), 4.38-4.45 (m, 2H), 4.01 (s,
3H) ppm.
[0395]
3-[(2-Trifluoromethoxy-phenylmethanesulfonyl)-(2,2-difluoro-ethyl)--
amino]-pyrazine-2-carboxylic acid methyl ester. 1H-NMR (400 MHz,
CDCl.sub.3): 8.57 (d, 1H), 8.46 (d, 1H), 7.48-7.50 (m, 1H),
7.30-7.41 (m, 2H), 7.17-7.22 (m, 1H), 5.96-6.26 (tt, 1H), 4.51 (s,
2H), 4.17-4.25 (m, 2H), 4.00 (s, 3H) ppm.
[0396]
3-[(2-Trifluoromethyl-phenylmethanesulfonyl)-(2,2-difluoro-ethyl)-a-
mino]-pyrazine-2-carboxylic acid methyl ester. 1H-NMR (400 MHz,
CDCl.sub.3): 8.61 (d, 1H), 8.53 (d, 1H), 7.61-7.69 (m, 2H),
7.41-7.48 (m, 2H), 6.00-6.30 (tt, 1H), 4.63 (s, 2H), 4.27-4.35 (dt,
2H), 3.99 (s, 3H) ppm.
[0397]
3-[(2-Trifluoromethylthio-phenylmethanesulfonyl)-(2,2-difluoro-ethy-
l)-amino]-pyrazine-2-carboxylic acid methyl ester. 1H-NMR (400 MHz,
CDCl.sub.3): 8.62 (d, 1H), 8.55 (d, 1H), 7.77-7.79 (m, 1H),
7.59-7.62 (m, 1H), 7.40-7.49 (m, 2H), 5.98-6.27 (tt, 1H), 4.78 (s,
2H), 4.19-4.27 (m, 2H), 4.00 (s, 3H) ppm.
Example 2.7
Preparation of
3-[(2,4-dichloro-phenylmethanesulfonyl)-(2,2,2-trifluoro-ethyl)-amino]-py-
razine-2-carboxylic acid methyl ester and
3-(2,4-dichloro-phenyl)-4-(2,2,2-trifluoro-ethoxy)-1-(2,2,2-trifluoro-eth-
yl)-1H-2-thia-1,5,8-triaza-naphthalene 2,2-dioxide (Compound No.
C106 of Table C)
##STR00034##
[0399] To a solution of
3-(2,4-dichloro-phenylmethanesulfonylamino)-pyrazine-2-carboxylic
acid methyl ester (Example 2.1) (0.1 g) in acetonitrile (1 ml) was
added N,N-diisopropylethylamine ("Hunig's base") (0.051 ml) and
2,2,2-trifluoroethyltrifluoromethanesulfonate (0.123 g). The
reaction mixture was heated in a microwave at 120.degree. C. for 25
minutes. The reaction mixture was allowed to cool to ambient
temperature and then concentrated. The residue was purified by
column chromatography on silica gel (eluent: iso-hexane/ethyl
acetate 4:1) to give
3-[(2,4-dichloro-phenylmethanesulfonyl)-(2,2,2-trifluoro-ethyl)-amino]-py-
razine-2-carboxylic acid methyl ester (0.024 g). 1H-NMR (400 MHz,
CDCl.sub.3): 8.70 (d, 1H), 8.56 (d, 1H), 7.50 (s, 1H), 7.40-7.42
(m, 1H), 7.20-7.23 (m, 1H), 4.74 (s, 2H), 4.59-4.69 (m, 2H), 4.05
(s, 3H) ppm.
[0400] A cyclized by-product, Compound No. C106 of Table C, was
also isolated (0.046 g).
Example 2.8
Preparation of
3-[(2-chloro-5-trifluoromethylphenylmethanesulfonyl)-(2,2-dichloro-ethyl)-
-amino]-pyrazine-2-carboxylic acid methyl ester
##STR00035##
[0402] To a solution of
3-(2-chloro-5-trifluoromethyl-phenylmethanesulfonylamino)-pyrazine-2-carb-
oxylic acid methyl ester (Example 2.1) (0.5 g) in acetonitrile (5
ml) was added N,N-diisopropylethylamine ("Hunig's base") (0.71 ml)
at ambient temperature. The mixture was stirred for 5 minutes at
ambient temperature before dropwise addition of
2,2-dichloroethyltrifluoromethanesulfonate (0.603 g) at ambient
temperature. The reaction mixture was stirred at ambient
temperature for 20 hours. The reaction mixture was concentrated and
the residue purified by column chromatography on silica gel
(eluent: iso-hexane/ethyl acetate 4:1) to give
3-[(2-chloro-5-trifluoromethyl-phenylmethanesulfonyl)-(2,2-dichloro-ethyl-
)-amino]-pyrazine-2-carboxylic acid methyl ester as a white solid
(0.179 g). 1H-NMR (400 MHz, CDCl.sub.3): 8.61 (d, 1H), 8.51 (d,
1H), 7.73 (s, 1H), 7.53-7.59 (m, 2H), 5.99-6.02 (m, 1H), 4.71 (s,
2H), 4.58 (d, 2H), 4.02 (s, 3H) ppm.
Example 2.9
Preparation of
3-[(2-nitro-phenylmethanesulfonyl)-prop-2-ynyl-amino]-pyrazine-2-carboxyl-
ic acid methyl ester
##STR00036##
[0404] To a solution of
3-(2-nitro-phenylmethanesulfonylamino)-pyrazine-2-carboxylic acid
methyl ester (Example 2.1) (0.5 g) in tetrahydrofuran (7 ml) was
added polymer bound triphenyl phosphine (0.388 g) and
prop-2-yn-1-ol (0.066 g) at ambient temperature. The mixture was
cooled to 0-5.degree. C. under nitrogen atmosphere and
di-tert-butyl azodicarboxylate ("DBAD") was added dropwise. The
reaction mixture was allowed to warm slowly to ambient temperature
and stirred for 20 hours. Further polymer bound triphenyl phosphine
(0.9 g) was added and the reaction mixture stirred at ambient
temperature for a further 72 hours. The reaction was filtered to
remove the polymer and concentrated. The residue was purified by
column chromatography on silica gel (eluent: iso-hexane/ethyl
acetate 3:1) to give
3-[(2-nitro-phenylmethanesulfonyl)-prop-2-ynyl-amino]-pyrazine-2-car-
boxylic acid methyl ester (0.131 g). 1H-NMR (400 MHz, CDCl.sub.3):
8.64 (s, 2H), 7.99 (d, 1H), 7.48-7.64 (m, 3H), 5.29 (s, 2H), 4.60
(s, 2H), 3.96 (s, 3H), 2.35 (t, 1H) ppm.
[0405] The following compound was made using the same method:
[0406]
3-[(2,5-Dichloro-6-trifluoromethyl-phenylmethanesulfonyl)-prop-2-yn-
yl-amino]-pyrazine-2-carboxylic acid methyl ester. 1H-NMR (400 MHz,
CDCl.sub.3): 8.69 (s, 2H), 7.54-7.59 (m, 2H), 5.31 (s, 2H), 4.79
(d, 2H), 3.98 (s, 3H), 2.40 (t, 1H) ppm.
[0407] The following compound was made using the same method with
but-2-yn-1-ol as reagent:
[0408]
3-[(2,5-Dichloro-6-trifluoromethyl-phenylmethanesulfonyl)-but-2-yny-
l-amino]-pyrazine-2-carboxylic acid methyl ester. 1H-NMR (400 MHz,
CDCl.sub.3): 8.69-8.71 (m, 2H), 7.57-7.62 (m, 2H), 5.36 (s, 2H),
4.73-4.74 (m, 2H), 4.01 (s, 3H), 1.80 (t, 1H) ppm.
[0409] The following compound was made using the same method with
prop-2-en-1-ol as reagent:
[0410]
3-[(5-Chloro-2-trifluoromethyl-phenylmethanesulfonyl)-prop-2-en-ami-
no]-pyrazine-2-carboxylic acid methyl ester. 1H-NMR (400 MHz,
CDCl.sub.3): 8.62 (d, 1H), 8.59 (d, 1H), 7.69 (s, 1H), 7.63 (d,
1H), 7.42 (d, 1H), 5.92-6.02 (m, 1H), 5.17-5.33 (m, 2H), 4.62 (s,
2H), 4.57-4.58 (d, 2H), 4.02 (s, 3H) ppm.
[0411] The following compound was made using the same method with
2-methyl-prop-2-en-1-ol as reagent:
[0412]
3-[(2,3-Dichloro-phenylmethanesulfonyl)-(2-methyl-allyl)-amino]-pyr-
azine-2-carboxylic acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3):
8.50 (d, 1H), 8.49 (d, 1H), 7.41 (d, 1H), 7.36 (d, 1H), 7.11 (t,
1H), 5.01 (s, 1H), 4.85 (s, 1H), 4.69 (s, 2H), 4.60 (s, 2H), 4.00
(s, 3H), 1.87 (s, 3H) ppm.
Example 2.10
Preparation of
3-(2-chloro-5-trifluoromethyl-phenyl)-1-(2,2-difluoro-ethyl)-2,2-dioxo-1,-
2-dihydro-2-.lamda.-6-thia-1,5,8-triaza-naphthalen-4-ol (Compound
No. D16 of Table D)
##STR00037##
[0414] To a solution of
3-[(2-chloro-5-trifluoromethyl-phenylmethanesulfonyl)-(2,2-difluoro-ethyl-
)-amino]-pyrazine-2-carboxylic acid methyl ester (Example 2.6) (186
mg) in tetrahydrofuran (7.1 ml) under nitrogen atmosphere was added
in portions a solution of sodium hexamethyldisilazide ("NaHMDS")
(0.97 ml) (1M in THF) at ambient temperature. The reaction mixture
was stirred for 3 hours at ambient temperature. The reaction
mixture was acidified by addition of aqueous hydrochloric acid (1M)
(5 ml). The phases were separated and the aqueous phase extracted
with ethyl acetate. The combined organic extracts were washed three
times with de-ionized water, dried over magnesium sulfate and
concentrated to give Compound No. D16 of Table D (172 mg) as a pale
orange oil which crystallized on standing.
[0415] The following compounds were made using the same method:
Compound Nos. D1-D8, D10-D15, D17-D19, and D21-D60 of Table D.
[0416] On one occasion some rearrangement of the propargyl group
occurred which resulted in the formation a propa-1,2-dien-1-yl
group. The isomers could not be separated by column chromatography
and were isolated as a 1:1 mixture. Consequently, Compound No. D40
of Table D is a 1:1 mixture of
3-(2-nitro-phenyl)-2,2-dioxo-1-prop-2-ynyl-1,2-dihydro-2-.lamda.-6-thi-
a-1,5,8-triaza-naphthalen-4-ol and
3-(2-nitro-phenyl)-2,2-dioxo-1-propa-1,2-dienyl-1,2-dihydro-2-.lamda.-6-t-
hia-1,5,8-triaza-naphthalen-4-ol.
[0417] On one occasion some transesterification of an ethyl ester
group occurred which resulted in a mixture of compounds being
isolated which could not be separated by column chromatography.
Consequently, Compound No. D58 of Table D is a 3:1 mixture of
2-[1-(3,3-difluoro-propyl)-4-hydroxy-2,2-dioxo-1,2-dihydro-2-.lamda.-6-th-
ia-1,5,8-triaza-naphthalen-3-yl]-6-trifluoromethyl-nicotinic acid
ethyl ester and
2-[1-(3,3-difluoro-propyl)-4-hydroxy-2,2-dioxo-1,2-dihydro-2-.l-
amda.-6-thia-1,5,8-triaza-naphthalen-3-yl]-6-trifluoromethyl-nicotinic
acid methyl ester.
Example 2.11
Preparation of 2,2-dimethyl-propionic acid
3-(2-chloro-5-trifluoromethyl-phenyl)-1-(2,2-difluoro-ethyl)-2,2-dioxo-1,-
2-dihydro-2-.lamda.-6-thia-1,5,8-triaza-naphthalen-4-yl ester
(Compound No. C34 of Table C)
##STR00038##
[0419] To a solution of Compound No. D16 of Table D (Example 2.10)
(110 mg) in acetonitrile (1.6 ml) was added 4-dimethylaminopyridine
("DMAP") (5 mg) followed by 2,2-dimethylpropionyl chloride (65 pd).
The reaction mixture was heated in a microwave at 150.degree. C.
for 1500 seconds. The reaction mixture was concentrated and the
residue purified by column chromatography on silica gel (eluent:
ethyl acetate/hexane 1:9) to give Compound No. C34 of Table C (71
mg).
Example 2.12
Preparation of isobutyric acid
1-ethyl-2,2-dioxo-3-(2-trifluoromethyl-sulfanyl-phenyl)-1,2-dihydro-2-.la-
mda.-6-thia-1,5,8-triaza-naphthalen-4-yl ester (Compound No. C19 of
Table C)
##STR00039##
[0421] To a solution of Compound No. D7 of Table D (Example 2.10)
(110 mg) in dichloromethane (5 ml) was added pyridine (33 .mu.l)
followed by isobutyryl chloride (35 .mu.l). The reaction mixture
was stirred at ambient temperature for 3 hours. The reaction
mixture was concentrated and the residue purified by column
chromatography on silica gel (eluent: ethyl acetate/hexane 15:85)
to give Compound No. C19 of Table C (91 mg).
Example 2.13
Preparation of carbonic acid
1-(2,2-difluoro-ethyl)-3-(5-methyl-2-trifluoromethyl-phenyl)-2,2-dioxo-1,-
2-dihydro-2-.lamda.-6-thia-1,5,8-triaza-naphthalen-4-yl ester ethyl
ester (Compound No. C147 of Table C)
##STR00040##
[0423] To a solution of Compound No. D41 of Table D (Example 2.10)
(190 mg) in dichloromethane (5 ml) was added triethylamine (95
.mu.l) followed by ethyl chloroformate (52 .mu.l). The reaction
mixture was stirred at ambient temperature for 3 hours. The
reaction mixture was concentrated and the residue purified by
column chromatography on silica gel (eluent: ethyl acetate/hexane
15:85) to give Compound No. C147 of Table C (205 mg).
[0424] The following compounds were made using one of the methods
as described in Example 2.11, Example 2.12, or Example 2.13 using
isobutyryl chloride, 2,2-dimethylpropionyl chloride,
cyclopropanecarbonyl chloride, ethyl chloroformate, S-methyl
chlorothioformate, S-ethyl chlorothioformate or S-phenyl
chlorothioformate as reagent: Compound Nos. C1-C2, C4, C9, C14-C18,
C20-C28, C30-C33, C35-C39, C41, C43-C47, C49-055, C57, C59-C82,
C84-C94, C96-C105, C107-C115, C117-C120, C124-C135, C139-C146, and
C148-C149 of Table C.
[0425] On one occasion an impurity of starting material resulted in
a mixture of tert-butylcarbonyloxy- and methoxy-compounds being
isolated. Compound Nos. C40 and C41 of Table C were separated using
column chromatography.
[0426] On one occasion some elimination occurred from the
2,2-dichloro-ethyl group which resulted in the formation of an
(E,Z)-2-chloro-vinyl group. Compound Nos. C114 and C115 of Table C
were separated using column chromatography.
[0427] On one occasion some transesterification of an ethyl ester
group occurred which resulted in a mixture of compounds being
isolated which could not be separated by column chromatography.
Consequently, Compound No. C139 of Table C is a 2:1 mixture of
2-[1-(3,3-difluoro-propyl)-4-methylsulfanylcarbonyloxy-2,2-dioxo-1,2-dihy-
dro-2-.lamda.-6-thia-1,5,8-triaza-naphthalen-3-yl]-6-trifluoromethyl-nicot-
inic acid ethyl ester and
2-[1-(3,3-difluoro-propyl)-4-methylsulfanylcarbonyloxy-2,2-dioxo-1,2-dihy-
dro-2-.lamda.-6-thia-1,5,8-triaza-naphthalen-3-yl]-6-trifluoromethyl-nicot-
inic acid methyl ester.
3. Reactions that are Covered by Scheme 3
Example 3.1
Preparation of
3-(2-chloro-3,6-difluoro-phenyl)-2,2-dioxo-1,2-dihydro-2-.lamda.-6-thia-1-
,5,8-triaza-naphthalen-4-ol (Compound No. A2 of Table A)
##STR00041##
[0429]
3-(2-Chloro-3,6-difluoro-phenylmethanesulfonylamino)-pyrazine-2-car-
boxylic acid methyl ester (Example 2.1) (480 mg) was dissolved in
N,N-dimethylformamide (7.5 ml) and heated, under a nitrogen
atmosphere, to 40.degree. C. in order to obtain a complete
solution. Sodium hexamethyldisilazide ("NaHMDS") (3.9 ml) (1M in
THF) was added in one portion. The reaction mixture was heated to
40.degree. C. for 5 hours and then stored at ambient temperature
for 16 hours. The reaction mixture was partitioned between water
and dichloromethane. The phases were separated. The aqueous layer
was washed with dichloromethane. The aqueous layer was acidified
with aqueous hydrochloric acid (2M) to give a yellow solid. The
solid was isolated by filtration, washed with water and dried under
vacuum at 50.degree. C. to give Compound No. A2 of Table A (375 mg)
as a yellow solid.
[0430] The following compounds were made using the same method:
Compound Nos. A1 and A3-A6 of Table A.
Example 3.2
Preparation of 2,2-dimethyl-propionic
acid-3-(2-chloro-3,6-difluoro-phenyl)-2,2-dioxo-1,2-dihydro-2-.lamda.-6-t-
hia-1,5,8-triaza-naphthalen-4-yl ester (Compound No. B3 of Table
B)
##STR00042##
[0432] To a suspension of Compound No. A2 (Example 3.1) in
dichloromethane (10 ml) was added pyridine (0.205 ml) followed by
2,2-dimethylpropionyl chloride (0.15 ml). The reaction mixture was
heated to 40.degree. C. for 4 hours and then stored at ambient
temperature of 16 hours. The reaction mixture was partition between
dichloromethane (30 ml) and aqueous hydrochloric acid (2M) (30 ml).
The phases were separated. The aqueous layer was extracted with
ethyl acetate. The combined organic extracts were concentrated. The
residue was triturated with iso-hexane and dried under vacuum to
give Compound No. B3 of Table B (408 mg) as a yellow solid.
[0433] The following compounds were made using the same method:
Compound Nos. B1-B2 and B4-B6 of Table B.
4. Reactions that are Covered by Scheme 4
Example 4.1
Preparation of 2,2-dimethyl-propionic
acid-3-(2,4-dichloro-phenyl)-1-(2,2-difluoroethyl)-2,2-dioxo-1,2-dihydro--
2-.lamda.-6-thia-1,5,8-triaza-naphthalen-4-yl ester (Compound No.
C12 of Table C) and 2,2-dimethylpropionic
acid-3-(2,4-dichloro-phenyl)-8-(2,2-difluoroethyl)-2,2-dioxo-2,8-dihydro--
2-.lamda.-6-thia-1,5,8-triaza-naphthalen-4-yl ester
##STR00043##
[0435] To a solution of Compound No. B1 of Table B (Example 3.2)
(250 mg) in acetonitrile (4 ml) was added N,N-diisopropylethylamine
("Hunig's base") (0.2 ml) and 1,1-difluoro-2-iodoethane (224 mg).
The reaction mixture was heated in a microwave at 130.degree. C.
for 1500 seconds. The reaction mixture was concentrated and the
residue purified by column chromatography on silica gel (eluent:
ethyl acetate/dichloromethane 0:10 to 1:9) to give Compound No. C12
of Table C (7 mg).
[0436] The other isomer, 2,2-dimethylpropionic
acid-3-(2,4-dichloro-phenyl)-8-(2,2-difluoroethyl)-2,2-dioxo-2,8-dihydro--
2-.lamda.-6-thia-1,5,8-triaza-naphthalen-4-yl ester, was also
isolated (9 mg). 1H-NMR (400 MHz, CDCl.sub.3): 7.84 (d, 1H),
7.52-7.54 (m, 2H), 7.41-7.42 (m, 1H), 7.33-7.36 (m, 1H), 6.24-6.53
(tt, 1H), 4.56-4.65 (m, 2H), 1.10 (s, 9H) ppm.
[0437] The following compounds were made using the same method:
Compound Nos. C5-C8, C10-C11, C13, C116, and C121-C123 of Table
C.
Example 4.2
Preparation of
3-(2,3-dichloro-6-fluoro-phenyl)-1-(2,2-difluoro-ethyl)-2,2-dioxo-1,2-dih-
ydro-2-.lamda.-6-thia-1,5,8-triaza-naphthalen-4-ol (Compound No. D9
of Table D)
##STR00044##
[0439] To a solution of Compound No. C20 of Table C (Example 2.8)
(110 mg) in tetrahydrofuran (5 ml) was added potassium
trimethylsilanolate (40 mg). The reaction mixture was stirred at
ambient temperature for 16 hours. The reaction mixture was
acidified by addition of glacial acetic acid. The mixture was
concentrated and the residue purified by column chromatography on
silica gel (eluent: ethyl acetate/hexane 15:85 to 100:0) to give
Compound No. D9 of Table D (68 mg).
Example 4.3
Preparation of
3-(2,4-dichloro-phenyl)-4-methoxy-1-methyl-1H-2-thia-1,5,8-triazanaphthal-
en-2,2-dioxide (Compound No. C3 of Table C)
##STR00045##
[0441] To a solution of Compound No. D1 of Table D (Example 2.7)
(50.5 mg) in acetonitrile (4 ml) under a nitrogen atmosphere was
added potassium carbonate (19.5 mg) followed by methyl iodide (22
mg). The reaction mixture was heated in a microwave at 150.degree.
C. for 1800 seconds. The reaction mixture was acidified by addition
of aqueous hydrochloric acid (2M) and the mixture partitioned
between water and dichloromethane. The phases were separated and
the aqueous layer was extracted with further dichloromethane. The
combined organic extracts were dried over magnesium sulfate and
concentrated to give Compound No. C3 of Table C (38 mg) as a brown
solid.
5. Reactions that are Covered by Scheme 5
Example 5.1
Preparation of trifluoromethanesulfonic
acid-3-(4-chloro-2-trifluoromethyl-phenyl)-1-ethyl-2,2-dioxo-1,2-dihydro--
2-.lamda.-6-thia-1,5,8-triaza-naphthalen-4-yl ester (Compound No.
C29 of Table C)
##STR00046##
[0443] To a solution of Compound No. D10 of Table D (Example 2.7)
(100 mg) in dichloromethane (2 ml) was added
N,N-diisopropylethylamine ("Hunig's base") (64 .mu.l). The reaction
mixture was cooled to -78.degree. C. and trifluoromethanesulfonic
anhydride (64 .mu.l) was added in portions over a period of 5
minutes. The reaction mixture was stirred at -78.degree. C. for 1.5
hours and then allowed to warm to ambient temperature and stirred
for a further 2 hours. The reaction mixture was quenched by
addition of water. The mixture was extracted with dichloromethane.
The combined organic extracts were dried over magnesium sulfate and
concentrated. The residue was purified by column chromatography on
silica gel (eluent: ethyl acetate/hexane 1:4) to give Compound No.
C29 of Table C (15 mg) a yellow solid.
Example 5.2
Preparation of methanesulfonic acid
3-(2-chloro-5-trifluoromethyl-phenyl)-1-(2,2-difluoro-ethyl)-2,2-dioxo-1,-
2-dihydro-2-.lamda.-6-thia-1,5,8-triaza-naphthalen-4-yl ester
(Compound No. C83 of Table C)
##STR00047##
[0445] To a solution of Compound No. D16 of Table D (Example 2.7)
(610 mg) in dichloromethane (20 ml) was added triethylamine (390
.mu.l) followed by methanesulfonyl chloride (160 mg). The reaction
mixture was stirred at ambient temperature for 3 hours. The
reaction mixture was concentrated and the residue purified by
column chromatography on silica gel (eluent: dichloromethane) to
give Compound No. C83 of Table C (595 mg).
[0446] The following compound was made using the same method:
Compound No. C95 of Table C.
6. Reactions which are Covered by Scheme 6
Example 6.1
Preparation of 1-bromo-3-bromomethyl-2-chloro-4-fluoro-benzene
##STR00048##
[0448] A mixture of 3-bromo-2-chloro-6-fluoro-toluene (commercially
available) (8.0 g), N-bromosuccinimide ("NBS") (6.42 g) and benzoyl
peroxide (catalytic amount) in carbon tetrachloride (40 ml) was
heated to reflux. A 500 watt tungsten halogen lamp was used to
initiate the reaction. The reaction mixture was heated to reflux
and irradiated for 30 minutes. The reaction mixture was allowed to
cool to ambient temperature and then filtered. The filtrate was
concentrated to give a colorless oil which solidified on standing
to give 1-bromo-3-bromomethyl-2-chloro-4-fluoro-benzene as an
off-white solid (10.7 g). 1H-NMR (400 MHz, CDCl.sub.3): 7.58 (dd,
1H), 6.94 (t, 1H), 4.64 (d, 21-1) ppm.
7. Reactions that are Covered by Scheme 7
Example 7.1
Preparation of 2,2-dimethylpropionic
acid-3-(2,3'-dichloro-4-fluoro-biphenyl-3-yl)-1-(2,2-difluoroethyl)-2,2-d-
ioxo-1,2-dihydro-2-.lamda.-6-thia-1,5,8-triaza-naphthalen-4-yl
ester (Compound No. C42 of Table C)
##STR00049##
[0450] To Compound No. C35 of Table C (0.089 g) was added
successively 3-chloro-phenyl boronic acid (0.038 g), palladium(II)
acetate (0.0072 g),
2'-dicyclohexyl-phosphino-2,6-dimethoxy-3-sulfonato-1,1'-biphenyl
hydrate sodium salt ("sodium S-Phos sulfonate") (0.012 g) and
toluene (1 ml). To this mixture was added a solution of potassium
phosphate (0.070 g) in degassed water (0.2 ml). The mixture was
pre-stirred at ambient temperature for 3 minutes and then heated in
a microwave at 110.degree. C. for 900 seconds. The reaction mixture
was diluted with ethyl acetate and washed with aqueous hydrochloric
acid (2M). The organic phase was dried over magnesium sulfate and
concentrated. The residue was purified by reverse phase column
chromatography to give Compound No. C42 of Table C (15 mg).
[0451] The following compounds were made using the same method:
Compound Nos. C56 and C142 of Table C, and Compound No. D.sub.2O of
Table D.
8. Reactions that are Covered by Scheme 8
Example 8.1
Preparation of
C-(2,4-dichloro-phenyl)-N-(2-fluoro-ethyl)-methane-sulfonamide
##STR00050##
[0453] To a suspension of 2-fluoroethylamine hydrochloride (0.287
g) in dichloro-methane (4 ml) was added triethylamine (0.4 ml)
followed by (2,4-dichloro-phenyl)-methanesulfonyl chloride (Example
1.2) (0.25 g). The reaction mixture was stirred at ambient
temperature for 3 hours then left to stand at ambient temperature
for 16 hours. Dichloromethane (20 ml) was added to the reaction
mixture and the mixture was washed with water (20 ml). The phases
were separated and the organic layer was dried over magnesium
sulfate and concentrated to give
C-(2,4-dichloro-phenyl)-N-(2-fluoro-ethyl)-methanesulfonamide (15
mg) (60% pure). 1H-NMR (400 MHz, CDCl.sub.3): 7.47-7.51 (m, 2H),
7.29-7.32 (dd, 1H), 4.77 (bs, 1H), 4.49 (s, 2H), 4.51-4.53 (m, 1H),
4.39-4.42 (m, 1H), 3.33-3.36 (m, 1H), 3.27-3.29 (m, 1H) ppm.
Example 8.2
Preparation of isobutyric acid
3-(2,4-dichloro-phenyl)-1-(2-fluoroethyl)-2,2-dioxo-1,2-dihydro-2-.lamda.-
-6-thia-1,5,8-triaza-naphthalen-4-yl ester (Compound No. C58 of
Table C)
##STR00051##
[0455] To
C-(2,4-dichloro-phenyl)-N-(2-fluoro-ethyl)-methanesulfonamide
(Example 8.1) (0.231 g) was added successively
3-chloro-pyrazine-2-carboxylic acid methyl ester (0.151 g),
potassium carbonate (0.446 g) and N,N-dimethylformamide (2 ml). The
reaction mixture was heated in a microwave for 25 minutes at
120.degree. C. The reaction mixture was diluted with ethyl acetate
and washed with aqueous hydrochloric acid (2M). The organic
extracts were dried over magnesium sulfate and concentrated. The
residue was dissolved in acetonitrile (1 ml) and
4-dimethylaminopyridine ("DMAP") (1 mg) and 2,2-dimethylpropionyl
chloride (7 .mu.l) were added. The reaction mixture was heated in a
microwave at 120.degree. C. for 25 minutes. The reaction mixture
was concentrated and the residue purified by column chromatography
on silica gel (eluent: ethyl acetate/hexane 15:85) to give Compound
No. C58 of Table C (21 mg).
9. Reactions that are Covered by Scheme 9
Example 9.1
Preparation of
3-methoxylcarbonylmethanesulfonylamino-pyrazine-2-carboxylic acid
methyl ester
##STR00052##
[0457] A solution of chlorosulfonylacetyl chloride (3.0 g) in
dichloromethane (18 ml) was cooled to 0-5.degree. C. and a mixture
of methanol (0.83 ml) and triethylamine (2.87 ml) in
dichloromethane was added dropwise. The reaction mixture was
stirred at 0-5.degree. C. for one hour and then at ambient
temperature for a further hour. 3-Amino-pyrazine-2-carboxylic acid
methyl ester (2.34 g) was added followed by dropwise addition of a
solution of pyridine (6 ml) in dichloromethane (10 ml) over a
period of 5 minutes at ambient temperature. The reaction mixture
was stirred at ambient temperature for 23 hours. Dichloromethane
(50 ml) was added to the reaction mixture and the mixture was
washed with aqueous hydrochloric acid (2M) (4.times.30 ml). The
phases were separated and the organic layer was concentrated. The
residue was purified by column chromatography on silica gel
(eluent: ethyl acetate/dichloromethane from 0:10 to 1:9) to give
3-methoxy-carbonylmethanesulfonylamino-pyrazine-2-carboxylic acid
methyl ester (1.212 g). 1H-NMR (400 MHz, CDCl.sub.3): 10.52 (s,
1H), 8.53 (d, 1H), 8.45 (d, 1H), 4.64 (s, 2H), 4.07 (s, 3H), 3.80
(s, 3H) ppm.
[0458] The following compound was made using the same method:
[0459]
3-tert-Butoxycarbonylmethanesulfonylamino-pyrazine-2-carboxylic
acid methyl ester. 1H-NMR (400 MHz, CDCl.sub.3): 10.47 (s, 1H),
8.53 (s, 1H), 8.44 (s, 1H), 4.52 (s, 2H), 4.07 (s, 3H), 1.45 (s,
9H) ppm.
Example 9.2
Preparation of
3-[(2,2-difluoro-ethyl)-methoxycarbonylmethanesulfonylamino]-pyrazine-2-c-
arboxylic acid methyl ester
##STR00053##
[0461] To a solution of
3-methoxycarbonylmethanesulfonylamino-pyrazine-2-carboxylic acid
methyl ester (Example 9.1) (1.212 g) in acetonitrile (12 ml) was
added N,N-diisopropylethylamine ("Hunig's base") (0.8 ml) at
ambient temperature. The mixture was stirred at ambient temperature
for 5 minutes before dropwise addition of a solution of
2,2-difluoroethyltrifluoromethanesulfonate (0.978 g) in
acetonitrile (5 ml) at ambient temperature. The reaction mixture
was stirred at ambient temperature for 20 hours. The reaction
mixture was concentrated and the residue partitioned between ethyl
acetate (30 ml) and aqueous sulfuric acid (2M) (30 ml). The phases
were separated and the organic layer was concentrated. The residue
was purified by column chromatography on silica gel (eluent: ethyl
acetate/hexane 1:2) to give
3-[(2,2-difluoro-ethyl)-methoxycarbonyl-methanesulfonyl-amino]-pyrazine-2-
-carboxylic acid methyl ester (0.819 g). 1H-NMR (400 MHz,
CDCl.sub.3): 8.70 (d, 1H), 8.65 (d, 1H), 6.06-6.29 (m, 1H),
4.32-4.38 (m, 2H), 4.18 (s, 2H), 4.02 (s, 3H), 3.78 (s, 3H)
ppm.
[0462] The following compound was made using the same method:
[0463]
3-[tert-Butoxycarbonylmethanesulfonyl-(2,2-difluoro-ethyl)-amino]-p-
yrazine-2-carboxylic acid methyl ester. 1H-NMR (400 MHz,
CDCl.sub.3): 8.69 (s, 1H), 8.65 (s, 1H), 6.18 (tt, 1H), 4.31-4.39
(m, 2H), 4.04 (s, 2H), 4.02 (s, 3H), 1.48 (s, 9H) ppm.
Example 9.3
Preparation of
1-(2,2-difluoro-ethyl)-4-hydroxy-2,2-dioxo-1,2-dihydro-2-.lamda.-6-thia-1-
,5,8-triaza-naphthalene-3-carboxylic acid methyl ester
##STR00054##
[0465] To a solution of
3-[(2,2-difluoro-ethyl)-methoxycarbonylmethanesulfonyl-amino]-pyrazine-2--
carboxylic acid methyl ester (Example 9.2) (0.819 g) in
tetrahydrofuran (40 ml) under nitrogen atmosphere was added in
portions a solution of sodium hexamethyldisilazide ("NaHMDS") (5.8
ml) (1M in THF) at ambient temperature. The reaction mixture was
stirred for 3 hours at ambient temperature. The reaction was
quenched by addition of glacial acetic acid and the mixture was
concentrated. The residue was partitioned between ethyl acetate (30
ml) and aqueous hydrochloric acid (2M) (15 ml). The phases were
separated and the organic layer was concentrated to give
1-(2,2-difluoro-ethyl)-4-hydroxy-2,2-dioxo-1,2-dihydro-2-.lamda.-6-thia-1-
,5,8-triaza-naphthalene-3-carboxylic acid methyl ester (0.520 g).
1H-NMR (400 MHz, CDCl.sub.3): 8.65 (d, 1H), 8.59 (d, 1H), 6.02-6.32
(m, 1H), 4.60-4.67 (m, 2H), 4.13 (s, 3H) ppm.
[0466] The following compounds were made using the same method:
[0467]
1-(2,2-Difluoro-ethyl)-4-hydroxy-2,2-dioxo-1,2-dihydro-2-.lamda.-6--
thia-1,5,8-triaza-naphthalene-3-carboxylic acid tert-butyl ester.
1H-NMR (400 MHz, CDCl.sub.3): 8.61 (m, 1H), 8.56 (m, 1H), 6.04-6.35
(tt, 1H), 4.59-4.66 (dt, 2H), 1.67 (s, 9H) ppm.
[0468]
4-Hydroxy-2,2-dioxo-1,2-dihydro-2-.lamda.-6-thia-1,5,8-triaza-napht-
halene-3-carboxylic acid ethyl ester. 1H-NMR (400 MHz,
d.sub.6-DMSO): 8.24 (d, 1H), 8.14 (d, 1H), 4.31 (q, 2H), 1.28 (t,
3H) ppm.
Example 9.4
Preparation of
1-(2,2-difluoro-ethyl)-2,2-dioxo-2,3-dihydro-1H-2-.lamda.-6-thia-1,5,8-tr-
iaza-naphthalen-4-one
##STR00055##
[0470] To a solution of
1-(2,2-difluoro-ethyl)-4-hydroxy-2,2-dioxo-1,2-dihydro-2-.lamda.-6-thia-1-
,5,8-triaza-naphthalene-3-carboxylic acid methyl ester (0.520 g)
(Example 9.3) in ethanol (3 ml) was added aqueous hydrochloric acid
(2M) (1 ml). The mixture was heated in a microwave for 20 minutes
at 150.degree. C. twice. The reaction mixture was concentrated to
give
1-(2,2-difluoro-ethyl)-2,2-dioxo-2,3-dihydro-1H-2-.lamda.-6-thia-1,5,8-tr-
iaza-naphthalen-4-one (0.203 g). 1H-NMR (400 MHz, CDCl.sub.3): 8.66
(d, 1H), 8.61 (d, 1H), 6.03-6.33 (m, 1H), 4.61 (s, 2H), 4.54-4.61
(m, 2H) ppm.
Example 9.5
Preparation of isobutyric acid
3-(2-chloro-4-methyl-phenyl)-1-(2,2-difluoro-ethyl)-2,2-dioxo-1,2-dihydro-
-2-.lamda.-6-thia-1,5,8-triaza-naphthalen-4-yl ester (Compound No.
C136 of Table C)
##STR00056##
[0472] A mixture of 2-chloro-4-methyl-phenyl lead triacetate (0.153
g),
1-(2,2-difluoro-ethyl)-2,2-dioxo-2,3-dihydro-1H-2-.lamda.-6-thia-1,5,8-tr-
iaza-naphthalen-4-one (Example 9.4) (0.070 g) and
4-dimethylaminopyridine ("DMAP") (0.169 g) in anhydrous chloroform
(2 ml) and toluene (1 ml) under a nitrogen atmosphere was heated to
reflux for four hours. Isobutyryl chloride (53 .mu.l) was added and
the reaction mixture heated to reflux for a further two hours. The
reaction mixture was then allowed to cool to ambient temperature
and diluted with dichloromethane and aqueous hydrochloric acid
(2M). The solids were removed by filtration and the filtrate was
separated. The aqueous layer was extracted with further
dichloromethane. The combined organic extracts were concentrated.
The residue was purified by column chromatography on silica gel
(eluent: ethyl acetate/hexane 1:6) to give Compound No. C136 of
Table C (0.019 g).
[0473] The following compounds were made using the same method:
Compound Nos. C48, C137 and C138 of Table C.
10. Reactions which are Covered by Scheme 10
Example 10.1
Preparation of
3-(2-chloro-5-trifluoromethyl-phenyl)-1-(2,2-difluoro-ethyl)-2,2-dioxo-5--
oxy-1,2-dihydro-2-.lamda.-6-thia-1,5,8-triaza-naphthalen-4-ol
(Compound No. E1 of Table E)
##STR00057##
[0475] A mixture of Compound No. D16 of Table D (0.869 g) and
freshly ground urea hydrogen peroxide (1.430 g) was stirred in
dichloromethane (50 ml) and trifluoroacetic anhydride ("TFAA")
(0.868 ml) was added dropwise at ambient temperature. The reaction
mixture was stirred at ambient temperature for 72 hours. The
reaction mixture was quenched by addition of aqueous sodium
metabisulfite (1M) (50 ml). The phases were separated and the
organic phase was dried over magnesium sulfate and concentrated to
give Compound No. E1 of Table E (0.118 g).
11. Separation of Atropisomers
Example 11.1
Separation of the atropisomers of
3-(2-chloro-6-trifluoromethyl-phenyl)-1-(2,2-difluoro-ethyl)-2,2-dioxo-1,-
2-dihydro-2-.lamda.-6-thia-1,5,8-triaza-naphthalen-4-ol
[0476] A sample of
3-(2-chloro-6-trifluoromethyl-phenyl)-1-(2,2-difluoro-ethyl)-2,2-dioxo-1,-
2-dihydro-2-.lamda.-6-thia-1,5,8-triaza-naphthalen-4-ol was
subjected to preparative chromatography (100 mg).
Preparative Method:
Column: 250.times.20 mm CHIRALPAK.RTM. AS-H 5 .mu.m
[0477] Eluent: heptane/ethanol/trifluoroacetic acid (80:20:0.1)
Flow rate: 20 ml/min
Detection: UV 260 nm
Temperature: 21.degree. C.
Analytical Method:
Column: 250.times.4.6 mm CHIRALPAK.RTM. AS-H 5 .mu.m
[0478] Eluent: heptane/ethanol/trifluoroacetic acid (80:20:0.1)
Flow rate: 1 ml/min
Detection: DAD 230 nm
Temperature: 25.degree. C.
[0479] Compound No. D61 of Table D (atropisomer A, unknown
stereochemistry) was obtained in >92% chemical purity and
>99% enantiomeric excess (47 mg); this compound has a retention
time of 8.16 minutes. Compound No. D62 of Table D (atropisomer B,
unknown stereochemistry) was obtained in >97% chemical purity
and >99% enantiomeric excess (40 mg); this compound has a
retention time of 10.59 minutes.
TABLE-US-00010 TABLE A Compounds of formula (A'), i.e. a compound
of formula (I) wherein R.sup.1, R.sup.2 and R.sup.3 is hydrogen,
R.sup.5 is hydroxy, and R.sup.4 has the values as described in the
table below. ##STR00058## Compound 1H-NMR (400 MHz, CDCl.sub.3
except where indicated; No. R.sup.4 chemical shifts in ppm) A1
2,4-di-Cl-phenyl- d.sub.6-DMSO: 8.17 (d, 1 H), 7.81 (d, 1 H ), 7.66
(m, 1 H), 7.45-7.57 (m, 2 H). A2 2-Cl-3,6-di-F-phenyl-
d.sub.6-DMSO: 11.04 (bs, 1 H), 8.18 (d, 1 H), 8.09 (d, 1 H),
7.54-7.58 (m, 1 H), 7.33-7.38 (m, 1 H). A3 2-F.sub.3CO-phenyl-
d.sub.6-DMSO: 10.63 (bs, 1 H), 8.14 (d, 1 H), 8.06 (d, 1 H),
7.56-7.61 (m, 2 H), 7.43-7.47 (m, 2 H). A4 3,4-di-Cl-phenyl-
d.sub.6-DMSO: 10.80 (bs, 1 H), 8.10 (d, 1 H), 8.03 (d, 1 H), 7.84
(m, 1 H), 7.73-7.76 (m, 1 H), 7.62-7.65 (m, 1 H). A5
2-F.sub.3C-phenyl- d.sub.6-DMSO: 10.55 (bs, 1 H), 8.15 (d, 1 H),
8.07 (d, 1 H), 7.84 (d, 1 H), 7.76 (t, 1 H), 7.68 (t, 1 H), 7.57
(d, 1 H). A6 2-Cl--5-F.sub.3C-phenyl- Compound used crude. Key: bs
= broad singlet; d = doublet; t = triplet; m = multiplet.
TABLE-US-00011 TABLE B Compounds of formula (B'), i.e. a compound
of formula (I) wherein R.sup.1, R.sup.2 and R.sup.3 are hydrogen,
and R.sup.4 and R.sup.5 have the values as described in the table
below. ##STR00059## Compound 1H-NMR (400 MHz, CDCl.sub.3 except No.
R.sup.4 R.sup.5 where indicated; chemical shifts in ppm) B1
2,4-di-Cl-phenyl- t-Bu--(CO)O-- d.sub.4-MeOH: 8.03 (d, 1 H), 7.96
(d, 1 H), 7.65 (m, 1H), 7.45-7.52 (m, 2 H), 1.09 (s, 9 H). B2
2,4-di-Cl-phenyl- i-Pr(CO)O-- d.sub.6-DMSO: 8.15 (d, 1 H), 8.07 (d,
1 H), 7.85 (m, 1 H), 7.42 (d, 1 H), 2.65 (sept, 1 H), 0.95 (d, 3
H), 0.85 (d, 3 H). B3 2-Cl-3,6-di-F-phenyl- t-Bu--(CO)O
d.sub.6-DMSO: 8.20 (d, 1 H), 8.11 (d, 1 H), 7.67-7.72 (m, 1 H),
7.46-7.51 (m, 1 H), 1.01 (s, 9 H). B4 3,4-di-Cl-phenyl- t-Bu(CO)O--
d.sub.6-DMSO: 8.14 (d, 1 H), 8.07 (d, 1 H), 7.83 (d, 1 H), 7.67 (m,
1 H), 7.48-7.51 (m, 1 H), 1.13 (s, 9 H). B5 2-F.sub.3C-phenyl-
i-Pr(CO)O-- 8.90 (bs, 1 H), 7.79-7.81 (d, 2 H), 7.56- 7.70 (m, 4
H), 2.59-2.68 (m, 1 H), 1.24 (d, 3 H), 1.00 (d, 3 H). B6
2-Cl--5-F.sub.3C-phenyl- i-Pr(CO)O-- 8.11 (d, 1 H), 8.04 (d, 1 H),
7.85-7.89 (m, 1 H), 7.68 (m, 2 H), 2.64-2.72 (m, 1H), 0.97-1.07 (m,
6 H). Key: s = singlet; bs = broad singlet; d = doublet; sept =
septet; m = multiplet; Pr = propyl; Bu = butyl.
TABLE-US-00012 TABLE C Compounds of formula (C'), i.e. a compound
of formula (I) wherein R.sup.1 and R.sup.2 are hydrogen, and
R.sup.3, R.sup.4 and R.sup.5 have the values as described in the
table below. ##STR00060## 1H-NMR (400 MHz, CDCl.sub.3 Compound
except where indicated; No. R.sup.3 R.sup.4 R.sup.5 chemical shifts
in ppm) C1 Me 2,4-di-Cl-phenyl- c-Pr--(CO)O-- 8.43 (d, 1 H), 8.46
(d, 1 H), 7.60 (m, 1 H), 7.50 (d, 1 H), 7.37-7.40 (dd, 1 H), 3.70
(s, 3 H), 1.70-1.75 (m, 1 H), 0.96-1.06 (m, 4 H). C2 Me
2,4-di-Cl-phenyl- t-Bu--(CO)O-- 8.45 (d, 1 H), 8.40 (d, 1 H), 7.58
(d, 1 H), 7.51 (d, 1 H), 7.36-7.39 (m, 1 H), 3.70 (s, 3 H), 1.14
(s, 9 H). C3 Me 2,4-di-Cl-phenyl- MeO-- 8.51 (d, 1 H), 8.50 (d, 1
H), 7.55-7.59 (m, 2 H), 7.38- 7.41 (m, 1 H), 3.84 (s, 3 H), 3.66
(s, 3 H). C4 Me 2-Cl-3,6-di-F-phenyl- t-Bu--(CO)O-- 8.49 (d, 1 H),
8.44 (d, 1 H), 7.28-7.33 (m, 1 H), 7.12- 7.17 (m, 1 H), 3.73 (s, 3
H), 1.15 (s, 9 H). C5 Et 2,4-di-Cl-phenyl- t-Bu--(CO)O-- 8.45 (d, 1
H), 8.41 (d, 1 H), 7.57 (m, 1 H), 7.51 (m, 1 H), 7.36-7.38 (dd, 1
H), 4.39 (q, 2 H), 1.49 (t, 3 H), 1.14 (s, 9 H). C6 Et
2,4-di-Cl-phenyl- i-Pr--(CO)O-- 8.46 (d, 1 H), 8.41 (d, 1 H), 7.57
(d, 1 H), 7.50 (d, 1 H), 7.36-7.38 (dd, 1 H), 4.34- 4.44 (m, 2 H),
2.72 (sept, 1 H), 1.50 (t, 3 H), 1.12 (d, 3 H), 1.07 (d, 3 H). C7
Et 2-Cl-3,6-di-F-phenyl- t-Bu--(CO)O-- 8.49 (d, 1 H), 8.44 (d, 1
H), 7.27-7.32 (m, 1 H), 7.11- 7.16 (m, 1 H), 4.41 (q, 2 H), 1.49
(t, 3 H), 1.15 (s, 9 H). C8 Me 3,4-di-Cl-phenyl- t-Bu--(CO)O-- 8.45
(d, 1 H), 8.41 (d, 1 H), 7.65 (d, 1 H), 7.57 (d, 1 H), 7.43-7.46
(m, 1 H), 3.70 (s, 3 H), 1.25 (s, 9 H). C9 Me 2-Cl-3,6-di-F-phenyl-
i-Pr--(CO)O-- 8.50 (d, 1 H), 8.44 (d, 1 H), 7.29-7.34 (m, 1 H),
7.12- 7.17 (m, 1 H), 3.73 (s, 3 H), 2.74 (sept, 1 H), 1.12 (d, 3
H), 1.10 (d, 3 H). C10 Et 3,4-di-Cl-phenyl- t-Bu--(CO)O-- 8.44 (d,
1 H), 8.40 (d, 1 H), 7.65 (d, 1 H), 7.56 (d, 1 H), 7.43-7.46 (m, 1
H), 4.37 (q, 2 H), 1.51 (t, 3 H), 1.25 (s, 9 H). C11
MeO--H.sub.2C-- 2,4-di-Cl-phenyl- t-Bu--(CO)O-- 8.53 (d, 1 H), 8.50
(d, 1 H), 7.57 (d, 1 H), 7.50 (d, 1 H), 7.37-7.40 (m, 1 H), 5.67-
5.82 (m, 2 H), 3.52 (s, 3 H), 1.15 (s, 9 H). C12
F.sub.2HC--H.sub.2C-- 2,4-di-Cl-phenyl- t-Bu--(CO)O-- 8.50 (d, 1
H), 8.48 (d, 1 H), 7.58 (d, 1 H), 7.50 (d, 1 H), 7.38-7.40 (m, 1
H), 6.10- 6.37 (tt, 1 H), 4.54-4.79 (m, 2 H), 1.15 (s, 9 H). C13 Et
2-F.sub.3CO-phenyl- i-Pr--(CO)O-- 8.45 (d, 1 H), 8.40 (d, 1 H),
7.53-7.63 (m, 2 H), 7.38- 7.43 (m, 2 H), 4.30-4.46 (m, 2 H), 2.71
(sept, 1 H), 1.48 (t, 3 H), 1.12 (d, 3 H), 1.08 (d, 3 H). C14 Et
3-F.sub.3C-phenyl- t-Bu--(CO)O-- 8.45 (d, 1 H), 8.41 (d, 1 H),
7.75-7.82 (m, 3 H), 7.61- 7.65 (m, 1 H), 4.38 (q, 2 H), 1.52 (t, 3
H), 1.19 (s, 9 H). C15 Et 4-Cl--2-F.sub.3C-phenyl- t-Bu--(CO)O--
8.46 (d, 1 H), 8.42 (d, 1 H), 7.81-7.82 (m, 1 H), 7.60- 7.66 (m, 2
H), 4.29-4.48 (m, 2 H), 1.46 (t, 3 H), 1.08 (s, 9 H). C16 Et
2,3-di-Cl--6-F-phenyl- t-Bu--(CO)O-- 8.49 (d, 1 H), 8.44 (d, 1 H),
7.57-7.61 (m, 1 H), 7.11- 7.16 (m, 1 H), 4.41 (q, 2 H), 1.49 (t, 3
H), 1.14 (s, 9 H). C17 Et 2-Cl--6-F.sub.3C-phenyl- t-Bu--(CO)O--
8.48 (d, 1 H), 8.43 (d, 1 H), 7.74-7.78 (m, 2 H), 7.55- 7.60 (m, 1
H), 4.38 (q, 2 H), 1.50 (t, 3 H), 1.07 (s, 9 H). C18
F.sub.2HC--H.sub.2C-- 2-F.sub.3CS-phenyl- i-Pr--(CO)O-- 8.51 (d, 1
H), 8.49 (m, 1 H), 7.90-7.92 (m, 1 H), 7.59- 7.67 (m, 3 H),
6.12-6.42 (tt, 1 H), 4.74-4.85 (m, 1 H), 4.49-4.60 (m, 1 H), 2.68
(sept, 1 H), 1.08 (d, 3 H), 1.01 (d, 3 H). C19 Et
2-F.sub.3CS-phenyl- i-Pr--(CO)O-- 8.46 (d, 1 H), 8.42 (d, 1 H),
7.89-7.91 (m, 1 H), 7.57- 7.67 (m, 3 H), 4.32-4.48 (m, 2 H), 2.67
(sept, 1 H), 1.50 (t, 3 H), 1.07 (d, 3 H), 1.00 (d, 3 H). C20
F.sub.2HC--H.sub.2C-- 2,3-di-Cl--6-F-phenyl- t-Bu--(CO)O-- 8.53 (d,
1 H), 8.51 (d, 1 H), 7.59-7.63 (m, 1 H), 7.13- 7.17 (m, 1 H),
6.09-6.39 (tt, 1 H), 4.62-4.72 (m, 2 H), 1.14 (s, 9 H). C21
F.sub.2HC--H.sub.2C-- 2-F.sub.3CO-phenyl- t-Bu--(CO)O-- 8.49 (d, 1
H), 8.47 (d, 1 H), 7.55-7.61 (m, 2 H), 7.39- 7.43 (m, 2 H),
6.06-6.37 (tt, 1 H), 4.69-4.80 (m, 1 H), 4.49-4.61 (m, 1 H), 1.15
(s, 9 H). C22 F.sub.2HC--H.sub.2C-- 2-F.sub.3CO-phenyl-
i-Pr--(CO)O-- 8.50 (d, 1 H), 8.47 (d, 1 H), 7.55-7.61 (m, 2 H),
7.40- 7.45 (m, 2 H), 6.07-6.37 (tt, 1 H), 4.68-4.79 (m, 1 H),
4.50-4.61 (m, 1 H), 2.72 (sept, 1 H), 1.13 (d, 3 H), 1.09 (d, 3 H).
C23 MeO--H.sub.2C-- 2-F.sub.3CS-phenyl- t-Bu--(CO)O-- 8.52 (d, 1
H), 8.51 (d, 1 H), 7.89-7.91 (m, 1 H), 7.58- 7.67 (m, 3 H),
5.67-5.84 (m, 2 H), 3.55 (s, 3 H), 1.10 (s, 9 H). C24 Et
2-Cl--6-F--3-MeO-phenyl- t-Bu--(CO)O-- 8.47 (d, 1 H), 8.42 (d, 1
H), 7.02-7.14 (m, 2 H), 4.37 (q, 2 H), 3.92 (t, 3 H), 1.49 (t, 3
H), 1.12 (s, 9 H). C25 F.sub.2HC--H.sub.2C--
2-Cl--6-F--3-MeO-phenyl- t-Bu--(CO)O-- 8.51 (d, 1 H), 8.49 (d, 1
H), 7.04-7.15 (m, 2 H), 6.09- 6.40 (tt, 1 H), 4.61-4.72 (m, 2 H),
3.93 (t, 3 H), 1.13 (s, 9 H). C26 Et 3,4-di-Cl-phenyl-
i-Pr--(CO)O-- 8.45 (d, 1 H), 8.41 (d, 1 H), 7.66 (d, 1 H), 7.57 (d,
1 H), 7.42-7.45 (m, 1 H), 4.37 (q, 2 H), 2.80 (sept, 1 H), 1.51 (t,
3 H), 1.20-1.21 (m, 6 H). C27 MeO--H.sub.2C-- 2,4-di-Cl-phenyl-
i-Pr--(CO)O-- 8.53 (d, 1 H), 8.51 (d, 1 H), 7.58 (d, 1 H), 7.50 (d,
1 H), 7.37-7.40 (m, 1 H), 5.67- 5.82 (m, 2 H), 3.52 (s, 3 H), 2.73
(sept, 1 H), 1.13 (d, 3 H), 1.09 (d, 3 H). C28
F.sub.2HC--H.sub.2C-- 2,6-di-Cl-phenyl- t-Bu--(CO)O-- 8.52 (d, 1
H), 8.49 (d, 1 H), 7.47-7.49 (m, 2 H), 7.36- 7.40 (m, 1 H),
6.12-6.43 (tt, 1 H), 4.64-4.71 (m, 2 H), 1.11 (s, 9 H). C29 Et
4-Cl--2-F.sub.3C-phenyl- F.sub.3C--(SO.sub.2)O-- 8.61 (s, 2 H),
7.85-7.86 (m, 1 H), 7.68-7.74 (m, 2 H), 4.32-4.49 (m, 2 H), 1.48
(t, 3 H). C30 Et 2-Cl--6-F.sub.3C-phenyl- i-Pr--(CO)O-- 8.48 (d, 1
H), 8.43 (d, 1 H), 7.74-7.78 (m, 2 H), 7.56- 7.60 (m, 1 H), 4.38
(q, 2 H), 2.67 (sept, 1 H), 1.50 (t, 3 H), 1.04 (d, 3 H), 1.02 (d,
3 H). C31 F.sub.2HC--H.sub.2C-- 2-Cl--6-F.sub.3C-phenyl-
t-Bu--(CO)O-- 8.51 (m, 1 H), 8.49 (m, 1 H), 7.76-7.79 (m, 2 H),
7.58-7.61 (m, 1 H), 6.17- 6.41 (tt, 1 H), 4.60-4.65 (m, 2 H), 1.07
(s, 9 H). C32 F.sub.2HC--H.sub.2C-- 2,3-di-Cl--6-F-phenyl-
EtS--(CO)O-- 8.59 (d, 1 H), 8.54 (d, 1 H), 7.61-7.65 (m, 1 H),
7.14- 7.18 (m, 1 H), 6.08-6.38 (tt, 1 H), 4.57-4.76 (m, 2 H), 2.86
(q, 2 H), 1.27 (t, 3 H). C33 Et 2-Cl--5-F.sub.3C-phenyl-
t-Bu--(CO)O-- 8.47 (d, 1 H), 8.42 (d, 1 H), 7.81 (m, 1 H),
7.66-7.71 (m, 2 H), 4.35-4.46 (m, 2 H), 1.51 (t, 3 H), 1.10 (s, 9
H). C34 F.sub.2HC--H.sub.2C-- 2-Cl--5-F.sub.3C-phenyl-
t-Bu--(CO)O-- 8.52 (d, 1 H), 8.50 (d, 1 H), 7.80 (m, 1 H),
7.68-7.74 (m, 2 H), 6.11-6.41 (tt, 1 H), 4.54-4.80 (m, 2 H), 1.11
(s, 9 H). C35 F.sub.2HC--H.sub.2C-- 3-Br--2-Cl--6-F-phenyl-
t-Bu--(CO)O-- 8.52 (d, 1 H), 8.51 (d, 1 H), 7.76-7.79 (m, 1 H),
7.06- 7.11 (m, 1 H), 6.09-6.39 (tt, 1 H), 4.62-4.72 (m, 2 H), 1.14
(s, 9 H). C36 F.sub.2HC--H.sub.2C-- 2,3-di-Cl--6-F-phenyl-
i-Pr--(CO)O-- 8.51-8.53 (m, 2 H), 7.60- 7.63 (m, 1 H), 7.13-7.17
(m, 1 H), 6.09-6.39 (tt, 1 H), 4.58-4.76 (m, 2 H), 2.74 (sept, 1
H), 1.12 (d, 3 H), 1.10 (d, 3 H). C37 F.sub.2HC--H.sub.2C--
2,3,6-tri-Cl-phenyl- EtS--(CO)O-- 8.58 (d, 1 H), 8.53 (d, 1 H),
7.57 (d, 1 H), 7.44 (d, 1 H), 6.10-6.41 (tt, 1 H), 4.63- 4.71 (m, 2
H), 2.85 (q, 2 H), 1.27 (t, 3 H). C38 F.sub.2HC--H.sub.2C--
2,3,6-tri-Cl-phenyl- i-Pr--(CO)O-- 8.51-8.53 (m, 2 H), 7.56 (d, 1
H), 7.43 (d, 1 H), 6.12- 6.42 (tt, 1 H), 4.63-4.71 (m, 2 H), 2.73
(sept, 1 H), 1.10 (d, 3 H), 1.08 (d, 3 H). C39
F.sub.2HC--H.sub.2C-- 2-Br-phenyl- i-Pr--(CO)O-- 8.50 (d, 1 H),
8.48 (d, 1 H), 7.74 (d, 1 H), 7.53-7.55 (m, 1 H), 7.35-7.46 (m, 2
H), 6.11-6.42 (tt, 1 H), 4.73- 4.84 (m, 1 H), 4.52-4.63 (m, 1 H),
2.69 (sept, 2 H), 1.07 (d, 3 H), 1.01 (d, 3 H). C40 Me
2-Cl-quinolin-3-yl- MeO-- 8.54 (d, 1 H), 8.53 (d, 1 H), 8.45 (s, 1
H), 8.10 (d, 1 H), 7.91 (d, 1 H), 7.84 (dt, 1 H), 7.65 (dt, 1 H),
3.95 (s, 3 H), 3.70 (s, 3 H). C41 Me 2-Cl-quinolin-3-yl-
t-Bu--(CO)O-- 8.49 (d, 1 H), 8.44 (m, 2 H), 8.09 (d, 1 H),
7.83-7.94 (m, 2 H), 7.63-7.67 (m, 1 H), 3.75 (s, 3 H), 1.08 (s, 9
H). C42 F.sub.2HC--H.sub.2C-- 2-Cl--6-F-3- (3'-Cl--Ph)-phenyl-
t-Bu--(CO)O-- 8.53 (d, 1 H), 8.51 (d, 1 H), 7.45-7.49 (m, 1 H),
7.37- 7.40 (m, 3 H), 7.22-7.29 (m, 2 H), 6.10-6.40 (tt, 1 H),
4.64-4.73 (m, 2 H), 1.16 (s, 9 H). C43 Et 2-F--6-F.sub.3C-phenyl-
t-Bu--(CO)O-- 8.47 (d, 1 H), 8.43 (d, 1 H), 7.63-7.65 (m, 2 H),
7.42- 7.46 (m, 1 H), 4.36-4.42 (m, 2 H), 1.48 (t, 3 H), 1.08 (s, 9
H). C44 F.sub.2HC--H.sub.2C-- 2,5-bis-F.sub.3C-phenyl-
t-Bu--(CO)O-- 8.53 (d, 1 H), 8.51 (d, 1 H), 7.90-7.99 (m, 3 H),
6.10- 6.40 (tt, 1 H), 4.53-4.84 (m, 2 H), 1.10 (s, 9 H). C45 Et
2,4-di-Cl--5-F-phenyl- t-Bu--(CO)O-- 8.47 (d, 1 H), 8.42 (d, 1 H),
7.62 (d, 1 H), 7.40 (d, 1 H), 4.34-4.44 (m, 2 H), 1.50 (t, 3 H),
1.17 (s, 9 H). C46 Et 2,5-bis-F.sub.3C-phenyl- t-Bu--(CO)O-- 8.49
(d, 1 H), 8.44 (d, 1 H), 7.91-7.99 (m, 3 H), 4.30- 4.49 (m, 2 H),
1.48 (t, 3 H), 1.04 (s, 9 H). C47 F.sub.2HC--H.sub.2C--
2,4-di-Cl--5-F-phenyl- t-Bu--(CO)O-- 8.51 (d, 1 H), 8.49 (d, 1 H),
7.63 (d, 1 H), 7.39 (d, 1 H), 6.08-6.39 (tt, 1 H), 4.53- 4.78 (m, 2
H), 1.18 (s, 9 H). C48 F.sub.2HC--H.sub.2C--
2,6-di-Et--4-Me-phenyl- i-Pr--(CO)O-- 8.47 (d, 1 H), 8.44 (d, 1 H),
7.04 (s, 2 H), 6.09-6.39 (tt, 1 H), 4.62-4.70 (dt, 2 H), 2.60-2.72
(m, 5 H), 2.37 (s, 3 H), 1.20 (t, 6 H), 0.98 (d, 6 H). C49
F.sub.2HC--H.sub.2C-- 2,6-di-Br-phenyl- i-Pr--(CO)O-- 8.52 (d, 1
H), 8.50 (d, 1 H), 7.70 (d, 2 H), 7.22 (t, 1 H), 6.17-6.47 (tt, 1
H), 4.63- 4.71 (dt, 2 H), 2.73 (sept, 2 H), 1.07 (d, 6 H). C50 Et
2,5-di-Cl--6-F.sub.3C-phenyl- i-Pr--(CO)O-- 8.49 (d, 1 H), 8.44 (d,
1 H), 7.75 (d, 1 H), 7.69 (d, 1 H), 4.38 (q, 2 H), 2.69 (sept, 2
H), 1.50 (t, 3 H), 1.06 (d, 3 H), 1.05 (d, 3 H). C51 Et
2-Cl--5-I-phenyl- i-Pr--(CO)O-- 8.47 (d, 1 H), 8.42 (d, 1 H), 7.85
(d, 1 H), 7.73-7.76 (dd, 1 H), 7.27 (d, 1 H), 4.32-4.46 (m, 2 H),
2.72 (sept, 2 H), 1.50 (t, 3 H), 1.11 (d, 3 H), 1.07 (d, 3 H). C52
F.sub.2HC--H.sub.2C-- 2,5-di-Cl--6-F.sub.3C-phenyl- t-Bu--(CO)O--
8.52 (d, 1 H), 8.51 (d, 1 H), 7.77 (d, 1 H), 7.70 (d, 1 H),
6.13-6.44 (tt, 1 H), 4.58- 4.66 (m, 2 H), 1.09 (s, 9 H). C53
F.sub.2HC--H.sub.2C-- 2,5-di-Cl--6-F.sub.3C-phenyl- i-Pr--(CO)O--
8.52 (d, 1 H), 8.51 (d, 1 H), 7.77 (d, 1 H), 7.70 (d, 1 H),
6.14-6.44 (tt, 1 H), 4.57- 4.66 (m, 2 H), 2.69 (sept, 2 H), 1.07
(d, 3 H), 1.06 (d, 3 H). C54 F.sub.2HC--H.sub.2C--
2-Cl--5-I-phenyl- i-Pr--(CO)O-- 8.51 (d, 1 H), 8.48 (d, 1 H), 7.84
(d, 1 H), 7.75-7.77 (dd, 1 H), 7.28 (d, 1 H), 6.10-6.40 (tt, 1 H),
4.68- 4.79 (m, 1 H), 4.53-4.64 (m, 1 H), 2.71 (sept, 2 H), 1.12 (d,
3 H), 1.08 (d, 3 H). C55 F.sub.2HC--H.sub.2C-- 2-Cl--5-I-phenyl-
t-Bu--(CO)O-- 8.51 (d, 1 H), 8.48 (d, 1 H), 7.84 (d, 1 H),
7.75-7.77 (dd, 1 H), 7.28 (d, 1 H), 6.10-6.40 (tt, 1 H), 4.68- 4.79
(m, 1 H), 4.53-4.64 (m, 1 H), 1.14 (s, 9 H). C56
F.sub.2HC--H.sub.2C-- 2-Cl--5-(3'- Cl--Ph)-phenyl- t-Bu--(CO)O--
8.51 (d, 1 H), 8.48 (d, 1 H), 7.73 (m, 1 H), 7.63 (m, 1 H), 7.55
(m, 1 H), 7.34- 7.46 (m, 4 H), 6.12-6.42 (m, 1 H), 4.71-4.82 (m, 1
H), 4.54-4.66 (m, 1 H), 1.12 (s, 9 H). C57 F.sub.3C--H.sub.2C--
2,4-di-Cl-phenyl- i-Pr--(CO)O-- 8.53 (d, 1 H), 8.51 (d, 1 H), 7.59
(m, 1 H), 7.46 (d, 1 H), 7.38 (dd, 1 H), 4.88-5.06 (m, 2 H), 2.73
(sept, 1 H), 1.14 (d, 3 H), 1.08 (d, 3 H). C58
F.sub.2HC--H.sub.2C-- 2,4-di-Cl-phenyl- i-Pr--(CO)O-- 8.46 (s, 2
H), 7.58 (d, 1 H), 7.50 (d, 1 H), 7.38 (dd, 1 H), 4.52-4.86 (m, 4
H), 2.73 (sept, 1 H), 1.12 (d, 3 H), 1.08 (d, 3 H). C59
F.sub.2HC--H.sub.2C-- 2-Br--5-F.sub.3C-phenyl- i-Pr--(CO)O-- 8.53
(d, 1 H), 8.51 (d, 1 H), 7.89 (d, 1 H), 7.78 (m, 1 H), 7.63-7.65
(dd, 1 H), 6.12- 6.42 (ttf, 1 H), 4.73-4.84 (m, 1 H), 4.52-4.64 (m,
1 H), 2.71 (sept, 1 H), 1.08 (d, 3 H), 1.03 (d, 3 H). C60
F.sub.2HC--H.sub.2C-- 2-Br--5-F.sub.3C-phenyl- EtS--(CO)O-- 8.59
(d, 1 H), 8.53 (d, 1 H), 7.90 (d, 1 H), 7.79 (m, 1 H), 7.64-7.66
(dd, 1 H), 6.11- 6.41 (tt, 1 H), 4.74-4.85 (m, 1 H), 4.51-4.63 (m,
1 H), 2.77-2.92 (m, 2 H), 1.25 (t, 3 H). C61 F.sub.2HC--H.sub.2C--
2-F.sub.3C-phenyl- i-Pr--(CO)O-- 8.50 (d, 1 H), 8.47 (d, 1 H),
7.82-7.85 (m, 1 H), 7.63- 7.70 (m, 3 H), 6.07-6.37 (m, 1 H),
4.78-4.88 (m, 1 H), 4.44-4.55 (m, 1 H), 2.65 (sept, 1 H), 1.02 (d,
3 H), 0.95 (d, 3 H). C62 F.sub.2HC--H.sub.2C-- 2-F.sub.3C-phenyl-
t-Bu--(CO)O-- 8.50 (d, 1 H), 8.48 (d, 1 H), 7.82-7.85 (m, 1 H),
7.64- 7.69 (m, 3 H), 6.06-6.37 (m, 1 H), 4.79-4.90 (m, 1 H),
4.44-4.56 (m, 1 H), 1.04 (s, 9 H). C63 Et 2-F.sub.3C-phenyl-
i-Pr--(CO)O-- 8.46 (d, 1 H1), 8.42 (d, 1 H), 7.81-7.83 (m, 1 H),
7.63- 7.67 (m, 3 H), 4.30-4.48 (m, 2 H), 2.64 (sept, 1 H), 1.47 (t,
3 H), 1.02 (d, 3 H), 0.94 (d, 3 H). C64 Et 2-F.sub.3C-phenyl-
t-Bu--(CO)O-- 8.46 (d, 1 H), 8.42 (d, 1 H), 7.81-7.83 (m, 1 H),
7.63- 7.67 (m, 3 H), 4.32-4.47 (m, 2 H), 1.47 (t, 3 H), 1.04 (s, 9
H). C65 F.sub.2HC--H.sub.2C-- 2-nitro-phenyl- i-Pr--(CO)O-- 8.50
(d, 1 H), 8.49 (d, 1 H), 8.26 (d, 1 H), 7.71-7.81 (m, 3 H),
6.15-6.46 (m, 1 H), 4.76-4.87 (m, 1 H), 4.43- 4.55 (m, 1 H), 2.68
(sept, 1 H), 1.09 (d, 3 H), 1.05 (d, 3 H). C66
F.sub.2HC--H.sub.2C-- 2-nitro-phenyl- t-Bu--(CO)O-- 8.51 (d, 1 H),
8.48 (d, 1 H), 8.25 (d, 1 H), 7.70-7.81 (m, 3 H), 6.15-6.46 (m, 1
H), 4.77-4.87 (m, 1 H), 4.44- 4.56 (m, 1 H), 1.10 (s, 9 H). C67 Et
2-nitro-phenyl- i-Pr--(CO)O-- 8.50 (d, 1 H), 8.45 (d, 1 H), 8.25
(d, 1 H), 7.71-7.80 (m, 3 H), 4.35-4.52 (m, 2 H), 2.72 (sept, 1 H),
1.55 (t, 3 H), 1.12 (d, 3 H), 1.08 (d, 3 H). C68
HC.ident.C--H.sub.2C-- 2-nitro-phenyl- i-Pr--(CO)O-- 8.53 (d, 1 H),
8.47 (d, 1 H), 8.23 (d, 1 H), 7.69-7.80 (m, 3 H), 5.02 (d, 2 H),
2.67 (sept, 1 H), 2.36 (t, 1 H), 1.08 (d, 3 H), 1.03 (d, 3 H). C69
Et 2-Br--5-F.sub.3C-phenyl- t-Bu--(CO)O-- 8.48 (d, 1 H), 8.43 (d, 1
H), 7.86-7.88 (m, 1 H), 7.79 (bs, 1 H), 7.59-7.62 (m, 1 H),
4.36-4.47 (m, 2 H), 1.51 (t, 3 H), 1.09 (s, 9 H). C70 Et
2-Br--5-F.sub.3C-phenyl- i-Pr--(CO)O-- 8.48 (d, 1 H), 8.44 (d, 1
H), 7.88 (d, 1 H), 7.79 (bs, 1 H), 7.60-7.62 (m, 1 H), 4.34-4.49
(m, 2 H), 2.70 (sept, 1 H), 1.52 (t, 3 H), 1.07 (d, 3 H), 1.01 (d,
3 H). C71 Et 2,3,6-tri-Cl-phenyl- EtS--(CO)O-- 8.51 (d, 1 H), 8.50
(d, 1 H), 7.55 (d, 1 H), 7.43 (d, 1 H), 4.41 (q, 2 H), 2.85 (q, 2
H), 1.50 (t, 3 H), 1.27 (t, 3 H). C72 Et 2,3,6-tri-Cl-phenyl-
t-Bu--(CO)O-- 8.49 (d, 1 H), 8.44 (d, 1 H), 7.53 (d, 1 H), 7.42 (d,
1 H), 4.41 (q, 2 H), 1.50 (t, 3 H), 1.13 (s, 9 H). C73
F.sub.2HC--H.sub.2C-- 2-Cl--3-F.sub.3C-phenyl- i-Pr--(CO)O-- 8.52
(d, 1 H), 8.50 (d, 1 H), 7.87 (d, 1 H), 7.76 (d, 1 H), 7.52 (t, 1
H), 6.10-6.41 (tt, 1 H), 4.54-4.81 (m, 2 H), 2.71 (sept, 1 H), 1.06
(d, 3 H), 1.02 (d, 3 H). C74 F.sub.2HC--H.sub.2C--
2-Cl--3-F.sub.3C-phenyl- t-Bu--(CO)O-- 8.52 (d, 1 H), 8.50 (d, 1
H), 7.87 (d, 1 H), 7.77 (d, 1 H), 7.52 (t, 1 H), 6.11-6.41 (tt, 1
H), 4.55-4.81 (m, 2 H), 1.10 (s, 9 H). C75 Et
2-Cl--3-F.sub.3C-phenyl- i-Pr--(CO)O-- 8.48 (d, 1 H), 8.43 (d, 1
H), 7.86 (d, 1 H), 7.77 (bs, 1 H), 7.51 (t, 1H), 4.34- 4.48 (m,
2H), 2.70 (sept, 1H), 1.51 (t, 3H), 1.06 (d, 3H), 1.01 (d, 3H). C76
Et 2-Cl--3-F.sub.3C-phenyl- t-Bu--(CO)O-- 8.47 (d, 1 H), 8.43 (d, 1
H), 7.85 (d, 1 H), 7.78 (bs, 1 H), 7.50 (t, 1 H), 4.36- 4.46 (m, 2
H), 1.51 (t, 3 H), 1.09 (s, 9 H).
C77 F.sub.2HC--H.sub.2C-- 2-F--6-F.sub.3C-phenyl- i-Pr--(CO)O--
8.56 (d, 1 H), 8.54 (d, 1 H), 7.70-7.72 (m, 2 H), 7.48- 7.53 (m, 1
H), 6.13-6.44 (tt, 1 H), 4.57-4.81 (m, 2 H), 2.73 (sept, 1 H), 1.09
(d, 3 H), 1.07 (d, 3 H). C78 F.sub.2HC--H.sub.2C--
2-F--6-F.sub.3C-phenyl- t-Bu--(CO)O-- 8.56 (d, 1 H), 8.54 (d, 1 H),
7.69-7.72 (m, 2 H), 7.48-53 (t, 1 H), 6.13-6.43 (tt, 1 H),
4.58-4.81 (m, 2 H), 1.13 (s, 9 H). C79 F.sub.2HC--H.sub.2C--
2,6-bis-F.sub.3C-phenyl- i-Pr--(CO)O-- 8.49 (d, 1 H), 8.48 (d, 1
H), 8.07 (d, 2 H), 7.82 (t, 1 H), 6.16-6.46 (tt, 1 H), 4.50- 4.58
(dt, 2 H), 2.64 (sept, 1 H), 1.07 (d, 6 H). C80
F.sub.2HC--H.sub.2C-- 2-Br--5-F.sub.3C-phenyl- t-Bu--(CO)O-- 8.52
(d, 1 H), 8.50 (d, 1 H), 7.89 (d, 1 H), 7.78 (s, 1 H), 7.61-7.64
(dd, 1 H), 6.12- 6.42 (tt, 1 H), 4.73-4.84 (m, 1 H), 4.53-4.64 (m,
1 H), 1.10 (s, 9 H). C81 F.sub.2HC--H.sub.2C-- 2-I-phenyl-
t-Bu--(CO)O-- 8.54 (d, 1 H), 8.51 (d, 1 H), 8.03 (d, 1 H),
7.49-7.57 (m, 2 H), 7.2 1-7.25 (dt, 1 H), 6.18-6.49 (tt, 1 H),
4.83- 4.94 (m, 1 H), 4.54-4.66 (m, 1 H), 1.13 (s, 9 H). C82
F.sub.2HC--H.sub.2C-- 2-I-phenyl- EtS--(CO)O-- 8.56 (d, 1 H), 8.50
(d, 1 H), 8.00 (d, 1 H), 7.47-7.55 (m, 2 H), 7.20-7.24 (dt, 1 H),
6.15-6.45 (tt, 1 H), 4.80- 4.91 (m, 1 H), 4.48-4.59 (m, 1 H),
2.81-2.87 (m, 2 H), 1.25 (t, 3 H). C83 F.sub.2HC--H.sub.2C--
2-Br--5-F.sub.3C-phenyl- Me--(SO.sub.2)O-- 8.62 (d, 1 H), 8.59 (d,
1 H), 7.88-7.92 (m, 2 H), 7.66- 7.69 (dd, 1 H), 6.11-6.41 (tt, 1
H), 4.77-4.87 (m, 1 H), 4.51-4.63 (m, 1 H), 3.38 (s, 3 H). C84
HC.ident.C--H.sub.2C-- 2,5-di-Cl--6-F.sub.3C-phenyl- i-Pr--(CO)O--
8.57 (d, 1 H), 8.51 (d, 1 H), 7.76 (d, 1 H), 7.70 (d, 1 H),
5.02-5.03 (m, 2 H), 2.69 (sept, 1 H), 2.33 (t, 1 H), 1.04-1.07 (dd,
6 H). C85 HC.ident.C--H.sub.2C-- 2,5-di-Cl--6-F.sub.3C-phenyl-
EtS--(CO)O-- 8.59 (d, 1 H), 8.57 (d, 1 H), 7.77 (d, 1 H), 7.70 (d,
1 H), 5.01-5.03 (m, 2 H), 2.83 (q, 1 H), 2.34 (t, 1 H), 1.30 (t, 3
H). C86 HC.ident.C--H.sub.2C-- 2,5-di-Cl--6-F.sub.3C-phenyl-
t-Bu--(CO)O-- 8.56 (d, 1 H), 8.51 (d, 1 H), 7.76 (d, 1 H), 7.70 (d,
1 H), 5.02-5.04 (m, 2 H), 2.33 (t, 1 H), 1.09 (s, 9 H). C87 Et
2-Cl--5-F.sub.3C-phenyl- EtS--(CO)O-- 8.51 (d, 1 H), 8.50 (d, 1 H),
7.82 (s, 1 H), 7.68-7.74 (m, 2 H), 4.33-4.38 (m, 2 H), 2.77-2.91
(m, 2 H), 1.26 (t, 3 H). C88 F.sub.2HC--H.sub.2C--
2,4-di-Cl--5-F-phenyl- EtS--(CO)O-- 8.58 (d, 1 H), 8.52 (d, 1 H),
7.65 (d, 1 H), 7.39 (d, 1 H), 6.08-6.38 (tt, 1 H), 4.51- 4.79 (m, 2
H), 2.86 (q, 2 H), 1.29 (t, 3 H). C89 Me 2-Cl--5-F.sub.3C-phenyl-
EtS--(CO)O-- 8.51 (d, 1 H), 8.49 (d, 1 H), 7.83 (bs, 1 H),
7.69-7.74 (m, 2 H), 3.73 (s, 3 H), 2.77-2.91 (m, 2 H), 1.25 (t, 3
H). C90 Me 2-Cl--5-F.sub.3C-phenyl- i-Pr--(CO)O-- 8.48 (d, 1 H),
8.43 (d, 1 H), 7.81 (bs, 1 H), 7.68-7.73 (m, 2 H), 3.73 (s, 3 H),
2.71 (sept, 1 H), 1.09 (d, 3 H), 1.03 (d, 3 H). C91
F.sub.2HC--H.sub.2C-- 2-Cl--5-F.sub.3C-phenyl- i-Pr--(CO)O-- 8.52
(d, 1 H), 8.51 (d, 1 H), 7.79 (bs, 1 H), 7.69-7.74 (m, 2 H),
6.11-6.41 (tt, 1 H), 4.69-4.80 (m, 1 H), 4.54-4.65 (m, 1 H), 2.71
(sept, 1 H), 1.09 (d, 3 H), 1.04 (d, 3 H). C92 Me
2,3,6-tri-Cl-phenyl- i-Pr--(CO)O-- 8.49 (d, 1 H), 8.44 (d, 1 H),
7.53-7.56 (d, 1 H), 7.41- 7.44 (d, 1 H), 3.73 (s, 3 H), 2.73 (sept,
1 H), 1.10 (d, 3 H), 1.08 (d, 3 H). C93 Me 2,3,6-tri-Cl-phenyl-
t-Bu--(CO)O-- 8.49 (d, 1 H), 8.44 (d, 1 H), 7.53-7.55 (d, 1 H),
7.41- 7.43 (d, 1 H), 3.73 (s, 3 H), 1.13 (s, 9 H). C94 Me
2,3,6-tri-Cl-phenyl- EtS--(CO)O-- 8.51 (d, 1 H), 8.50 (d, 1 H),
7.55-7.57 (d, 1 H), 7.42- 7.45 (d, 1 H), 3.73 (s, 3 H), 2.83-2.88
(q, 2 H), 1.27 (t, 3 H). C95 F.sub.2HC--H.sub.2C--
2-Cl--5-F.sub.3C-phenyl- Me--(SO.sub.2)O-- 8.62 (d, 1 H), 8.59 (d,
1 H), 7.89 (bs, 1 H), 7.71-7.78 (m, 2 H), 6.09-6.40 (tt, 1 H),
4.73-4.84 (m, 1 H), 4.53-4.65 (m, 1 H), 3.38 (s, 3 H). C96
Me--C.ident.C--H.sub.2C-- 2,5-di-Cl--6-F.sub.3C-phenyl-
t-Bu--(CO)O-- 8.56 (d, 1 H), 8.49 (d, 1 H), 7.75 (d, 1 H), 7.69 (d,
2 H), 4.97-5.00 (m, 2 H), 1.80 (t, 1 H), 1.09 (s, 9 H). C97
Me--C.ident.C--H.sub.2C-- 2,5-di-Cl--6-F.sub.3C-phenyl-
EtS--(CO)O-- 8.58 (d, 1 H), 8.54 (d, 1 H), 7.76 (d, 1 H), 7.70 (d,
2 H), 4.96-4.98 (m, 2 H), 2.83 (q, 2 H), 1.80 (t, 1 H), 1.31 (t, 3
H). C98 Et 2,3-di-Cl-phenyl- t-Bu--(CO)O-- 8.46 (d, 1 H), 8.42 (d,
1 H), 7.60 (d, 1 H), 7.49 (d, 1 H), 7.32 (t, 1 H), 4.35-4.46 (m, 2
H), 1.50 (t, 3 H), 1.11 (s, 9 H). C99 Et 2,3-di-Cl-phenyl-
EtS--(CO)O-- 8.52 (d, 1 H), 8.51 (d, 1 H), 7.66 (dd, 1 H), 7.53
(dd, 1 H), 7.38 (t, 1 H), 4.36- 4.51 (m, 2 H), 2.89 (q, 2 H), 1.54
(t, 3 H), 1.34 (t, 3 H). C100 F.sub.2HC--H.sub.2C--
2,3-di-Cl-phenyl- t-Bu--(CO)O-- 8.55 (d, 1 H), 8.52 (d, 1 H), 7.66
(dd, 1 H), 7.52 (dd, 1 H), 7.38 (t, 1 H), 6.14- 6.45 (tt, 1 H),
4.74-4.85 (m, 1 H), 4.5 8-4.69 (m, 1 H), 1.16 (s, 9 H). C101
F.sub.2HC--H.sub.2C-- 2,3-di-Cl-phenyl- EtS--(CO)O-- 8.61 (d, 1 H),
8.55 (d, 1 H), 7.68 (dd, 1 H), 7.52 (dd, 1 H), 7.39 (t, 1 H), 6.13-
6.43 (tt, 1 H), 4.74-4.85 (m, 1 H), 4.55-4.66 (m, 1 H), 2.89 (q, 2
H), 1.34 (t, 3 H). C102 F.sub.2HC--H.sub.2C-- 2,3-di-Cl-phenyl-
i-Pr--(CO)O-- 8.51 (d, 1 H), 8.49 (d, 1 H), 7.63 (dd, 1 H), 7.47
(dd, 1 H), 7.34 (t, 1 H), 6.10- 6.40 (tt, 1 H), 4.70-4.81 (m, 1 H),
4.53-4.64 (m, 1 H), 2.71 (sept, 2 H), 1.10 (d, 3 H), 1.05 (d, 3 H).
C103 F.sub.2HC--H.sub.2C-- 2,5-di-Cl--6-F.sub.3C-phenyl-
EtS--(CO)O-- 8.58 (d, 1 H), 8.53 (d, 1 H), 7.78 (d, 1 H), 7.71 (d,
2 H), 6.13-6.43 (tt, 1 H), 4.56- 4.66 (m, 2 H), 2.83 (q, 2 H), 1.25
(t, 3 H). C104 F.sub.3C--H.sub.2C-- 2,4-di-Cl-phenyl- t-Bu--(CO)O--
8.54 (d, 1 H), 8.50 (d, 1 H), 7.58 (d, 1 H), 7.46 (d, 1 H), 7.38
(dd, 1 H), 4.89-5.07 (m, 2 H), 1.15 (s, 9 H). C105
F.sub.2HC--H.sub.2C-- 2-Cl--6-F.sub.3C-phenyl- EtS--(CO)O-- 8.57
(d, 1 H), 8.52 (d, 1 H), 7.77-7.81 (m, 2 H), 7.60- 7.64 (m, 1 H),
6.13-6.43 (tt, 1 H), 4.53-4.71 (m, 2 H), 2.82 (q, 2 H), 1.26 (t, 3
H). C106 F.sub.3C--H.sub.2C-- 2,4-di-Cl-phenyl-
F.sub.3C--H.sub.2C--O-- 8.62 (d, 1 H), 8.57 (d, 1 H), 7.60 (d, 1
H), 7.45 (d, 1 H), 7.40 (dd, 1 H), 4.90-5.06 (m, 2 H), 4.71-4.80
(m, 1 H), 4.44-4.53 (m, 1 H). C107 F.sub.2HC--H.sub.2C--
3-Br--2-Cl--6-F-phenyl- EtS--(CO)O-- 8.58 (d, 1H), 8.53 (d, 1 H),
7.77-7.81 (m, 1 H), 7.08- 7.12 (m, 1 H), 6.07-6.38 (tt, 1 H),
4.57-4.75 (m, 2 H), 2.85 (q, 2 H), 1.27 (t, 3 H). C108 Et
5-Cl--2-F.sub.3C-phenyl- t-Bu--(CO)O-- 8.47 (d, 1 H), 8.43 (d, 1
H), 7.76 (d, 1 H), 7.66 (s, 1 H), 7.62 (d, 1 H), 4.30-4.48 (m, 2
H), 1.47 (t, 3 H), 1.08 (s, 9 H). C109 Et 5-Cl--2-F.sub.3C-phenyl-
EtS--(CO)O-- 8.50 (d, 1 H), 8.49 (d, 1 H), 7.77 (d, 1 H), 7.68 (s,
1 H), 7.64 (d, 1 H), 4.25-4.53 (m, 2 H), 2.79-2.90 (m, 2 H), 1.47
(t, 3 H), 1.30 (t, 3 H). C110 Et 5-Cl--2-F.sub.3C-phenyl-
i-Pr--(CO)O-- 8.48 (d, 1 H), 8.43 (d, 1 H), 7.76 (d, 1 H), 7.66 (s,
1 H), 7.62 (d, 1 H), 4.30-4.48 (m, 2 H), 2.68 (sept, 1 H), 1.47 (t,
3 H), 1.07 (d, 3 H), 1.01 (d, 3 H). C111 F.sub.2HC--H.sub.2C--
5-Cl--2-F.sub.3C-phenyl- t-Bu--(CO)O-- 8.52 (d, 1 H), 8.49 (d, 1
H), 7.77 (d, 1 H), 7.65 (s, 1 H), 7.64 (d, 1 H), 6.06-6.36 (m, 1
H), 4.78-4.88 (m, 1 H), 4.43-4.55 (m, 1 H), 1.08 (s, 9 H). C112
F.sub.2HC--H.sub.2C-- 5-Cl--2-F.sub.3C-phenyl- EtS--(CO)O-- 8.56
(d, 1 H), 8.51 (d, 1 H), 7.78 (d, 1 H), 7.67 (s, 1 H), 7.65 (d, 1
H), 6.06-6.36 (m, 1 H), 4.76-4.87 (m, 1 H), 4.42-4.53 (m, 1 H),
2.84- 2.95 (m, 2 H), 1.25 (t, 3 H). C113 F.sub.2HC--H.sub.2C--
5-Cl--2-F.sub.3C-phenyl- i-Pr--(CO)O-- 8.52 (d, 1 H), 8.50 (d, 1
H), 7.77 (d, 1 H), 7.65 (s, 1 H), 7.64 (d, 1 H), 6.06-6.37 (m, 1
H), 4.77-4.87 (m, 1 H), 4.43-4.55 (m, 1 H), 2.69 (sept, 1 H), 1.07
(d, 3 H), 1.02 (d, 3 H). C114 (E,Z)--ClHC.dbd.HC--
2-Cl--5-F.sub.3C-phenyl- i-Pr--(CO)O-- 8.51-8.53 (m, 2 H), 7.79 (s,
1 H), 7.69-7.75 (m, 2 H), 6.91-7.01 (m, 2 H), 2.71 (sept, 1 H),
1.09 (d, 3 H), 1.04 (d, 3 H). C115 Cl.sub.2HC--H.sub.2C--
2-Cl--5-F.sub.3C-phenyl- i-Pr--(CO)O-- 8.52-8.54 (m, 2 H), 7.78 (s,
1 H), 7.69-7.74 (m, 2 H), 6.20-6.24 (m, 1 H), 5.02- 5.07 (m, 1 H),
4.79-4.85 (m, 1 H), 2.71 (sept, 1 H), 1.09 (d, 3 H), 1.04 (d, 3 H).
C116 Cl.sub.2HC--H.sub.2C-- 2,4-di-Cl-phenyl- i-Pr--(CO)O--
8.50-8.52 (m, 2 H), 7.59 (s, 1 H), 7.47 (d, 1 H), 7.38 (d, 1 H),
6.18-6.21 (m, 1 H), 5.00-5.04 (m, 1 H), 4.80- 4.84 (m, 1 H), 2.72
(sept, 1 H), 1.13 (d, 3 H), 1.09 (d, 3 H). C117
F.sub.2HC--H.sub.2C-- 2-I-phenyl- i-Pr--(CO)O-- 8.51 (d, 1 H), 8.48
(d, 1 H), 7.99 (d, 1 H), 7.46-7.53 (m, 2 H), 7.18-7.22 (m, 1 H),
6.14-6.45 (tt, 1 H), 4.79- 4.90 (m, 1 H), 4.50-4.61 (m, 1 H), 2.69
(sept, 1 H), 1.06 (d, 3 H), 1.00 (d, 3 H). C118
H.sub.2C.dbd.HC--H.sub.2C-- 5-Cl--2-F.sub.3C-phenyl- t-Bu--(CO)O--
8.46 (d, 1 H), 8.44 (d, 1 H), 7.76 (d, 1 H), 7.65 (s, 1 H), 7.62
(d, 1 H), 5.99-6.08 (m, 1 H), 5.26-5.41 (m, 2 H), 4.90-4.93 (m, 2
H), 1.08 (s, 9 H). C119 H.sub.2C.dbd.HC--H.sub.2C--
5-Cl--2-F.sub.3C-phenyl- EtS--(CO)O-- 8.49-8.51 (m, 2 H), 7.77 (d,
1 H), 7.67 (s, 1 H), 7.64 (d, 1 H), 5.99-6.08 (m, 1 H), 5.26-5.41
(m, 2 H), 4.89- 4.92 (m, 2 H), 2.79-2.90 (m, 2 H), 1.26 (t, 3 H).
C120 F.sub.2HC--H.sub.2C-- 5-Cl--2-F.sub.3C-phenyl- EtO--(CO)O--
8.56 (d, 1 H), 8.53 (d, 1 H), 7.79 (d, 1 H), 7.68 (s, 1 H), 7.66
(d, 1 H), 6.06-6.36 (m, 1 H), 4.78-4.88 (m, 1 H), 4.42-4.54 (m, 1
H), 4.23 (q, 2 H), 1.27 (t, 3 H). C121 ClH.sub.2C--H.sub.2C--
2-F.sub.3C-phenyl- i-Pr--(CO)O-- 7.81 (d, 1 H), 7.77-7.80 (m, 1 H),
7.58-7.65 (m, 3 H), 7.54 (d, 1 H), 4.52-4.65 (m, 2 H), 4.09 (t, 2
H), 2.59 (sept, 1 H), 0.99 (d, 3 H), 0.88 (d, 3 H). C122
F.sub.2HC--F.sub.2C--H.sub.2C-- 2,4-di-Cl-phenyl- i-Pr--(CO)O--
8.57 (d, 1 H), 8.45 (d, 1 H), 7.58 (d, 1 H), 7.46 (d, 1 H), 7.38
(dd, 1 H), 5.79-6.09 (m, 1 H), 4.48-5.07 (m, 2 H), 2.74 (sept, 1
H), 1.08- 1.14 (m, 6 H). C123 ClH.sub.2C--H.sub.2C--
2-Cl--5-F.sub.3C-phenyl- i-Pr--(CO)O-- 8.45-8.48 (m, 2 H), 7.79 (s,
1 H), 7.68-7.73 (m, 2 H), 4.55-4.72 (m, 2 H), 3.88- 3.92 (m, 2 H),
2.70 (sept, 1 H), 1.13 (d, 3 H), 1.08 (d, 3 H). C124
F.sub.2HC--H.sub.2C-- 3-Cl--5-F.sub.3C-phenyl- EtO--(CO)O-- 8.57
(d, 1 H), 8.53 (d, 1 H), 7.78-7.79 (m, 2 H), 7.73 (s, 1 H),
6.12-6.42 (m, 1 H), 4.60-4.68 (dt, 2 H), 4.29 (q, 2 H), 1.33 (t, 3
H). C125 F.sub.2HC--H.sub.2C-- 2-Cl--6-F.sub.3C-phenyl-
PhS--(CO)O-- 8.60 (d, 1 H), 8.51 (d, 1 H), 7.78-7.81 (m, 2 H), 7.64
(t, 1 H), 7.32-7.42 (m, 5 H), 6.10-6.40 (tt, 1 H), 4.51- 4.68 (m, 2
H). C126 F.sub.2HC--H.sub.2C-- 2,3,6-tri-Cl-phenyl- PhS--(CO)O--
8.61 (d, 1 H), 8.53 (d, 1 H), 7.60 (d, 1 H), 7.35-7.47 (m, 6 H),
6.07-6.38 (tt, 1 H), 4.61-4.68 (dt, 2 H). C127
F.sub.2HC--H.sub.2C-- 2,4-bis-F.sub.3C-phenyl- i-Pr--(CO)O-- 8.53
(d, 1 H), 8.52 (d, 1 H), 8.09 (s, 1 H), 7.96 (d, 1 H), 7.83 (d, 1
H), 6.06-6.36 (tt, 1 H), 4.77-4.88 (m, 1 H), 4.45-4.56 (m, 1 H),
2.67 (sept, 1 H), 1.06 (d, 3 H), 0.99 (d, 3 H). C128
F.sub.2HC--H.sub.2C-- 2-cyano-phenyl- i-Pr--(CO)O-- 8.53 (d, 1 H),
8.51 (d, 1 H), 7.85 (d, 1 H), 7.72-7.75 (m, 2 H), 7.63-7.67 (m, 1
H), 6.16-6.46 (tt, 1 H), 4.67- 4.82 (m, 1 H), 4.52-4.64 (m, 1 H),
2.72 (sept, 1 H), 1.11 (d, 3 H), 1.05 (d, 3 H). C129
F.sub.2HC--H.sub.2C-- 2-Cl--6-F.sub.3C-phenyl- MeS--(CO)O-- 8.57
(d, 1 H), 8.52 (d, 1 H), 7.78 (t, 2 H), 7.62 (t, 1 H), 6.13-6.43
(tt, 1 H), 4.58- 4.66 (m, 2 H), 2.31 (s, 3 H). C130
F.sub.2HC--H.sub.2C-- 2,3,6-tri-Cl-phenyl- MeS--(CO)O-- 8.58 (d, 1
H), 8.53 (d, 1 H), 7.57 (d, 1 H), 7.44 (d, 1 H), 6.11-6.41 (tt, 1
H), 4.63- 4.71 (dt, 2 H), 2.34 (s, 3 H). C131 F.sub.2HC--H.sub.2C--
2,4-bis-F.sub.3C-phenyl- MeS--(CO)O-- 8.59 (d, 1 H), 8.54 (d, 1 H),
8.10 (s, 1 H), 7.97 (d, 1 H), 7.84 (d, 1 H), 6.06-6.37 (m, 1 H),
4.77-4.88 (m, 1 H), 4.44-4.55 (m, 1 H), 2.33 (s, 3 H). C132
F.sub.2HC--H.sub.2C-- 4-Br--2-F.sub.3C-phenyl- i-Pr--(CO)O-- 8.51
(d, 1 H), 8.49 (d, 1 H), 7.98 (d, 1 H), 7.82 (dd, 1 H), 7.53 (d, 1
H), 6.05- 6.35 (tt, 1 H), 4.76-4.87 (m, 1 H), 4.43-4.55 (m, 1 H),
2.68 (sept, 1 H), 1.08 (d, 3 H), 1.02 (d, 3 H). C133
F.sub.2HC--H.sub.2C-- 4-Br--2-F.sub.3C-phenyl- MeS--(CO)O-- 8.57
(d, 1 H), 8.52 (d, 1 H), 7.98 (d, 1 H), 7.84 (dd, 1 H), 7.54 (d, 1
H), 6.05- 6.35 (m, 1 H), 4.76-4.87 (m, 1 H), 4.42-4.54 (m, 1 H),
2.33 (s, 3 H). C134 F.sub.2HC--H.sub.2C--
2,3-di-Cl--6-F.sub.3C-phenyl- i-Pr--(CO)O-- 8.52 (d, 1 H), 8.51 (d,
1 H), 7.77 (d, 1 H), 7.70 (s, 1 H), 6.13-6.44 (tt, 1 H), 4.58- 4.66
(m, 2 H), 2.69 (sept, 1 H), 2.41 (s, 3 H), 1.07 (d, 3 H), 1.06 (d,
3 H). C135 F.sub.2HC--H.sub.2C-- 2,3-di-Cl--6-F.sub.3C-phenyl-
EtS--(CO)O-- 8.58 (d, 1 H), 8.53 (d, 1 H), 7.78 (d, 1 H), 7.71 (s,
1 H), 6.15-6.40 (m, 1 H), 4.54- 4.69 (m, 2 H), 2.84 (q, 2 H), 1.26
(t, 3 H). C136 F.sub.2HC--H.sub.2C-- 2-Cl--4-Me-phenyl-
i-Pr--(CO)O-- 8.49 (d, 1 H), 8.46 (d, 1 H), 7.42 (d, 1 H), 7.37 (s,
1 H), 7.19 (d, 1 H), 6.10-6.40 (m, 1 H), 4.68-4.79 (m, 1 H),
4.52-4.64 (m, 1 H), 2.71 (sept, 1 H), 2.41 (s, 3 H), 1.10 (d, 3 H),
1.05 (d, 3 H). C137 F.sub.2HC--H.sub.2C-- 2-F--6-MeO-phenyl-
i-Pr--(CO)O-- 8.48 (d, 1 H), 8.45 (d, 1 H), 7.41-7.47 (m, 1 H),
6.80- 6.84 (m, 2 H), 6.08-6.39 (m, 1 H), 4.51-4.69 (m, 2 H), 3.87
(s, 3 H), 2.72 (sept, 1 H), 1.12 (d, 6 H). C138
F.sub.2HC--H.sub.2C-- 2-F--5-MeO-phenyl- i-Pr(--CO)O-- 8.49 (d, 1
H), 8.46 (d, 1 H), 7.11-7.16 (m, 1 H), 7.00- 7.04 (m, 2 H),
6.12-6.43 (m, 1 H), 4.53-4.74 (m, 2 H), 3.82 (s, 3 H), 2.77 (sept,
1 H), 1.17 (d, 6 H). C139 F.sub.2HC--H.sub.2C--
3-EtO(CO)--6-F.sub.3C-pyrid- 2-yl- MeS--(CO)O-- 2:1 Mixture of
ethyl ester and methyl ester. Ethyl ester: 8.58-8.59 (m, 1 H), 8.55
(d, 1 H), 8.51-8.52 (m, 1 H), 7.89-7.92 (m, 1 H), 6.15- 6.47 (m, 1
H), 4.44-4.87 (m, 2 H), 4.28-4.37 (m, 2 H), 2.34 (s, 3 H), 1.27 (t,
3 H). Methyl ester: 8.58-8.59 (m, 1 H), 8.55 (d, 1 H), 8.51-8.52
(m, 1 H), 7.89-7.92 (m, 1 H), 6.15- 6.47 (m, 1 H), 4.44-4.87 (m, 2
H), 2.34 (s, 3 H), 3.86 (s, 3 H). C140
H.sub.2C.dbd.(Me)C--H.sub.2C-- 2,3-di-Cl-phenyl- t-Bu--(CO)O-- 8.44
(d, 1 H), 8.43 (d, 1 H), 7.60 (d, 1 H), 7.47 (d, 1 H), 7.31 (t, 1
H), 4.88-4.96 (m, 4 H), 1.81 (s, 3 H), 1.12 (s, 9 H). C141
F.sub.2HC--H.sub.2C-- 2-Cl--4-I-phenyl- t-Bu--(CO)O-- 8.48 (d, 1
H), 8.45 (d, 1 H), 7.93 (s, 1 H), 7.73 (d, 1 H), 7.26 (d, 1 H),
6.09-6.39 (m, 1 H), 4.52-4.77 (m, 2 H), 1.14 (s, 9 H). C142
F.sub.2HC--H.sub.2C-- 2-Cl-4-(4'-Cl--2'-F--Ph)- phenyl-
t-Bu--(CO)O-- 8.51 (m, 1 H), 8.47 (m, 1 H), 7.71 (s, 1 H), 7.62 (d,
1 H), 7.53 (d, 1 H), 7.34- 7.43 (m, 1 H), 7.22-7.26 (m, 2 H),
6.11-6.42 (m, 1 H), 4.55-4.81 (m, 2 H), 1.13 (s, 9 H). C143
F.sub.2HC--H.sub.2C-- 2-Cl--6-F--5-MeO-phenyl- i-Pr--(CO)O-- 8.51
(d, 1 H), 8.49 (d, 1 H), 7.28 (d, 1 H), 7.06 (t, 1 H), 6.10-6.40
(m, 1 H), 4.59- 4.75 (m, 2 H), 3.92 (s, 3 H), 2.73 (sept, 1 H),
1.10 (dd, 6 H). C144 F.sub.2HC--H.sub.2C-- 2-Cl--6-F--5-MeO-phenyl-
t-Bu--(CO)O-- 8.50 (d, 1 H), 8.48 (d, 1 H), 7.27 (d, 1 H), 7.05 (t,
1 H), 6.10-6.40 (m, 1 H), 4.62- 4.71 (m, 2 H), 3.91 (s, 3 H), 1.14
(s, 9 H). C145 F.sub.2HC--H.sub.2C-- 2-Cl--6-F--5-MeO-phenyl-
EtS--(CO)O-- 8.56 (d, 1 H), 8.51 (d, 1 H), 7.29 (d, 1 H), 7.07 (t,
1 H), 6.09-6.39 (m, 1 H), 4.57- 4.75 (m, 2 H), 3.92 (s, 3 H), 2.85
(q, 2 H), 1.26 (t, 3 H). C146 F.sub.2HC--H.sub.2C--
5-Me--2-F.sub.3C-phenyl- i-Pr--(CO)O-- 8.50 (d, 1 H), 8.48 (d, 1
H), 7.71 (d, 1 H), 7.44-7.45 (m, 2 H), 6.06-6.37 (m, 1 H),
4.79-4.89 (m, 1 H), 4.43- 4.54 (m, 1 H), 2.66 (sept, 1 H), 1.04 (d,
3 H), 0.97 (d, 3 H). C147 F.sub.2HC--H.sub.2C--
5-Me--2-F.sub.3C-phenyl- EtO--(CO)O-- 8.53 (d, 1 H), 8.51 (d, 1 H),
7.72 (d, 1 H), 7.47 (s, 1 H), 7.46 (d, 1 H), 6.06-6.37 (m, 1 H),
4.78-4.89 (m, 1 H), 4.41-4.53 (m, 1 H), 4.18- 4.23 (q, 2 H), 2.48
(s, 3 H), 1.25 (t, 3 H). C148 F.sub.2HC--H.sub.2C--
5-Me--2-F.sub.3C-phenyl- t-Bu--(CO)O-- 8.50 (d, 1 H), 8.47 (d, 1
H), 7.70 (d, 1 H), 7.45 (s, 1 H), 7.44 (d, 1 H), 6.06-6.36 (m, 1
H), 4.79-4.90 (m, 1 H), 4.42-4.54 (m, 1 H), 2.47 (s, 3 H), 1.05 (s,
9 H). C149 F.sub.2HC--H.sub.2C-- 3-Cl--5-F.sub.3C-phenyl-
i-Pr--(CO)O-- 8.52 (d, 1 H), 8.50 (d, 1 H), 7.76-7.77 (m, 2 H),
7.71 (s, 1H), 6.12-6.42 (m, 1 H), 4.60-4.68 (dt, 2H), 2.80 (sept, 1
H), 1.19-1.20 (d, 6H).
Key: s = singlet; bs = broad singlet; d = doublet; t = triplet; q =
quartet; dd = double doublet; dt = double triplet; tt = triple
triplet; sept = septet; m = multiplet; Me = methyl; Et = ethyl; Pr
= propyl; Bu = butyl.
TABLE-US-00013 TABLE D Compound of formula (D'), i.e. a compound of
formula (I) wherein R.sup.1 and R.sup.2 are hydrogen, R.sup.5 is
hydroxy, and R.sup.3 and R.sup.4 have the values as described in
the table below. (D') ##STR00061## 1H-NMR (400 MHz, CDCl.sub.3
except Compound where indicated; chemical shifts in No. R.sup.3
R.sup.4 ppm) D1 Me 2,4-di-Cl- 8.55 (d, 1H), 8.35 (d, 1H), 8.23 (bs,
phenyl- 1H), 7.58-7.60 (m, 2H), 7.37-7.40 (m, 1H), 3.68 (s, 3H). D2
Me 2-Cl-3,6-di- 8.59 (d, 1H), 8.38 (d, 1H), 8.24 (bs, F-phenyl-
1H), 7.27-7.33 (m, 1H), 7.12-7.18 (m, 1H), 3.70 (s, 3H). D3 Et
3-F.sub.3C- 8.55 (d, 1H), 8.36 (d, 1H), 8.32 (bs, phenyl- 1H),
7.92-8.00 (m, 2H), 7.60-7.72 (m, 2H), 4.38 (q, 2H), 1.50 (t, 3H).
D4 Et 2,3-di-Cl-6- d.sub.4-MeOH: 8.62 (d, 1H), 8.52 (d, 1H),
F-phenyl- 7.68-7.72 (m, 1H), 7.25-7.29 (m, 1H), 4.29-4.35 (m, 2H),
1.43 (t, 3H). D5 Et 2-F.sub.3CO- 8.56 (d, 1H), 8.36 (d, 1H), 8.18
(bs, phenyl- 1H), 7.70-7.72 (m, 1H), 7.52-7.56 (m, 1H), 7.39-7.43
(m, 2H), 4.32-4.41 (m, 2H), 1.48 (t, 3H). D6 Et 2-Cl-6-F.sub.3C-
8.58 (m, 1H), 8.37 (m, 1H), 7.74-7.79 phenyl- (m, 2H), 7.54-7.58
(m, 1H), 4.33-4.38 (m, 2H), 1.46 (t, 3H). D7 Et 2-F.sub.3CS- 8.56
(d, 1H), 8.36 (d, 1H), 7.89-7.91 phenyl- (m, 1H), 7.76-7.78 (m,
1H), 7.54-7.64 (m, 2H), 4.31-4.47 (m, 2H), 1.49 (t, 3H). D8 Et
3,4-di-Cl- 8.55 (d, 1H), 8.36 (d, 1H), 7.84 (m, phenyl- 1H),
7.54-7.60 (m, 2H), 4.36 (q, 2H), 1.49 (t, 3H). D9
F.sub.2HC--H.sub.2C-- 2,3-di-Cl-6- 8.62 (d, 1H), 8.49 (d, 1H),
7.59-7.63 F-phenyl- (m, 1H), 7.13-7.17 (m, 1H), 6.05-6.36 (tt, 1H),
4.60-4.79 (m, 2H). D10 Et 4-Cl-2-F.sub.3C- 8.57 (d, 1H), 8.37 (d,
1H), 8.10 (bs, phenyl- 1H), 7.83 (m, 1H), 7.64-7.69 (m, 2H),
4.28-4.47 (m, 2H), 1.46 (t, 3H). D11 F.sub.2HC--H.sub.2C--
2-Cl-6-F3C- 8.61 (m, 1H), 8.48 (m, 1H), 7.76-7.80 phenyl- (m, 2H),
7.56-7.60 (m, 1H), 6.08-6.32 (tt, 1H), 4.56-4.77 (m, 2H). D12
F.sub.2HC--H.sub.2C-- 2-Cl-6-F-3- 8.60 (d, 1H), 8.47 (d, 1H),
7.36-7.39 Me-phenyl- (m, 1H), 7.0-7.10 (m, 1H), 6.06-6.36 (tt, 1H),
4.60-4.79 (m, 2H), 2.43 (s, 3H). D13 Et 3-Br-2-Cl- 8.50 (bs, 1H),
8.05 (m, 1H), 7.76-7.80 6-F-phenyl- (m, 1H), 7.15-7.19 (m, 1H),
4.22-4.31 (m, 2H), 1.38-1.41 (t, 3H). D14 F.sub.2HC--H.sub.2C--
3-Br-2-Cl- 8.54 (m, 2H), 7.79-7.83 (m, 1H), 7.15- 6-F-phenyl- 7.20
(m, 1H), 6.08-6.38 (m, 1H), 4.51- 4.67 (m, 2H). D15 Et
2-Cl-5-F.sub.3C- 8.58 (d, 1H), 8.36 (d, 1H), 7.91 (m, phenyl- 1H),
7.66-7.71 (m, 2H), 4.36-4.42 (m, 2H), 1.50 (t, 3H). D16
F.sub.2HC--H.sub.2C-- 2-Cl-5-F.sub.3C- 8.61 (d, 1H), 8.48 (d, 1H),
7.89 (m, phenyl- 1H), 7.69-7.73 (m, 2H), 6.08-6.39 (tt, 1H),
4.57-4.82 (m, 2H). D17 F.sub.2HC--H.sub.2C-- 2,3,6-tri-Cl- 8.62 (d,
1H), 8.49 (d, 1H), 8.13 (bs, phenyl- 1H), 7.55 (d, 1H), 7.44 (d,
1H), 6.06- 6.36 (tt, 1H), 4.67-4.75 (m, 2H). D18
F.sub.2HC--H.sub.2C-- 2-Br- 8.58 (d, 1H), 8.45 (d, 1H), 8.15 (bs,
phenyl- 1H), 7.76 (d, 1H), 7.62-7.64 (m, 1H), 7.35-7.48 (m, 2H),
6.09-6.40 (tt, 1H), 4.54-4.65 (m, 1H), 4.75-4.86 (m, 1H). D19
F.sub.2HC--H.sub.2C-- 3-Cl-5-F.sub.3C- 8.60 (d, 1H), 8.48 (d, 1H),
8.41 (bs, phenyl- 1H), 7.89 (d, 2H), 7.70 (s, 1H), 6.07- 6.38 (tt,
1H), 4.63-4.71 (dt, 2H). D20 F.sub.2HC--H.sub.2C-- 2-Cl-6-F-3- 8.61
(d, 1H), 8.48 (d, 1H), 8.20 (bs, (3'-Cl--Ph)- 1H), 7.45-7.49 (m,
1H), 7.33-7.39 (m, phenyl- 3H), 7.23-7.27 (m, 2H), 6.06-6.37 (tt,
1H), 4.61-4.80 (m, 2H). D21 Et 2-F-6-F.sub.3C- 8.59 (d, 1H), 8.38
(d, 1H), 8.11 (bs, phenyl- 1H), 7.62-7.66 (m, 2H), 7.43-7.48 (m,
1H), 4.32-4.43 (m, 2H), 1.46 (t, 3H). D22 F.sub.2HC--H.sub.2C--
2,5-bis-F.sub.3C- 8.60 (d, 1H), 8.46 (d, 1H), 7.96-7.99 phenyl- (m,
2H), 7.89-7.91 (m, 1H), 6.03-6.33 (m, 1H), 4.79-4.90 (m, 1H),
4.43-4.55 (m, 1H). D23 Et 2,4-di-Cl-5- 8.50 (d, 1H), 8.28 (d, 1H),
7.55 (d, F-phenyl- 1H), 7.40 (d, 1H), 4.27-4.34 (m, 2H), 1.42 (t,
3H). D24 Et 2,5-bis-F.sub.3C- 8.59 (d, 1H), 8.37 (d, 1H), 7.96-7.98
phenyl- (m, 2H), 7.88-7.90 (m, 1H), 4.29-4.47 (m, 2H), 1.46 (t,
3H). D25 F.sub.2HC--H.sub.2C-- 2,4-di-Cl-5- 8.52 (d, 1H), 8.39 (d,
1H), 7.56 (d, F-phenyl- 1H), 7.38 (d, 1H), 6.00-6.30 (tt, 1H),
4.47-4.72 (m, 2H). D26 Et 2,5-di-Cl-6- 8.53-8.64 (m, 2H), 8.09 (bs,
1H), 7.80- F.sub.3C-phenyl- 7.89 (m, 2H), 4.29-4.33 (m, 2H), 1.38-
1.48 (m, 3H). D27 F.sub.2HC--H.sub.2C-- 2,5-di-Cl-6- 8.51-8.56 (m,
2H), 8.14 (bs, 1H), 7.76- F.sub.3C-phenyl- 7.82 (m, 2H), 6.08-6.38
(m, 1H), 4.53- 4.59 (m, 2H). D28 F.sub.2HC--H.sub.2C-- 2,6-di-Br-
8.41-8.46 (m, 2H), 7.66-7.70 (m, 2H), phenyl- 7.15-7.17 (m, 1H),
6.08-6.37 (m, 1H), 4.51-4.56 (m, 2H). D29 F.sub.2HC--H.sub.2C--
2-Cl-5-I- 8.59 (d, 1H), 8.46 (d, 1H), 8.21 (bs, phenyl- 1H), 7.93
(d, 1H), 7.74-7.77 (dd, 1H), 7.29 (d, 1H), 6.08-6.38 (tt, 1H),
4.71- 4.82 (m, 1H), 4.55-4.66 (m, 1H). D30 F.sub.2HC--H.sub.2C--
2-Br-5-F.sub.3C- 8.61 (d, 1H), 8.48 (d, 1H), 8.23 (bs, phenyl- 1H),
7.86-7.91 (m, 2H), 7.61-7.63 (dd, 1H), 6.09-6.39 (tt, 1H),
4.75-4.86 (m, 1H), 4.55-4.67 (m, 1H). D31 F.sub.2HC--H.sub.2C--
2-F.sub.3C- 8.56 (d, 1H), 8.43 (d, 1H), 7.83 (d, phenyl- 1H),
7.61-7.73 (m, 3H), 6.03-6.33 (m, 1H), 4.80-4.91 (m, 1H), 4.42-4.54
(m, 1H). D32 F.sub.2HC--H.sub.2C-- 2-nitro- 8.57 (d, 1H), 8.44 (d,
1H), 8.15 (d, phenyl- 1H), 7.74-7.81 (m, 2H), 7.64-7.69 (m, 1H),
6.09-6.39 (m, 1H), 4.75-4.86 (m, 1H), 4.45-4.56 (m, 1H). D33 Et
2-F.sub.3C- 8.54 (d, 1H), 8.33 (d, 1H), 7.82 (d, phenyl- 1H),
7.59-7.74 (m, 3H), 4.28-4.46 (m, 2H), 1.45 (t, 3H). D34 Et 2-nitro-
8.56 (d, 1H), 8.36 (d, 1H), 8.15 (d, phenyl- 1H), 7.64-7.84 (m,
3H), 4.30-4.45 (m, 2H), 1.49 (t, 3H). D35 Et 2-Br-5-F.sub.3C- 8.58
(d, 1H), 8.37 (d, 1H), 8.23 (bs, phenyl- 1H), 7.87-7.89 (m, 2H),
7.59-7.61 (dd, 1H), 4.36-4.43 (m, 2H), 1.50 (t, 3H). D36 Et
2,3,6-tri-Cl- 8.59 (d, 1H), 8.39 (d, 1H), 8.11 (bs, phenyl- 1H),
7.53 (d, 1H), 7.43 (d, 1H), 4.39 (q, 2H), 1.48 (t, 3H). D37
F.sub.2HC--H.sub.2C-- 2-Cl-3-F.sub.3C- 8.57 (d, 1H), 8.45 (d, 1H),
7.83 (t, phenyl- 2H), 7.51 (t, 1H), 6.08-6.38 (tt, 1H), 4.54-4.80
(m, 2H). D38 Et 2-Cl-3-F.sub.3C- 8.56 (d, 1H), 8.35 (d, 1H), 7.84
(d, phenyl- 2H), 7.50 (t, 1H), 4.33-4.43 (m, 2H), 1.49 (t, 3H). D39
F.sub.2HC--H.sub.2C-- 2-F-6-F.sub.3C- 8.54 (d, 1H), 8.41 (d, 1H),
7.57-7.99 phenyl- (m, 2H), 7.38-7.42 (m, 1H), 5.96-6.26 (tt, 1H),
4.43-4.78 (m, 2H). D40 HC.ident.C--H.sub.2C-- 2-nitro- 1:1 Mixture
of prop-2-yn-1-yl isomer phenyl- and propa-1,2-dien-1-yl isomer.
Prop-2-yn-1-yl isomer: 8.43 (d, 1H), 8.41 (d, 1H), 8.16 (d, 1H),
7.65-7.84 (m, 3H), 5.02 (t, 2H), 2.34 (t, 3H). Propa-1,2-dien-1-yl
isomer: 8.64 (d, 1H), 8.59 (d, 1H), 8.16 (d, 1H), 7.65-7.84 (m,
3H), 6.70 (t, 1H), 5.49 (d, 2H). D41 F.sub.2HC--H.sub.2C-- 5-Me-2-
8.58 (d, 1H), 8.46 (d, 1H), 8.06 (s, F.sub.3C-phenyl- 1H), 7.72 (d,
1H), 7.52 (s, 1H), 7.43 (d, 1H), 6.03-6.33 (m, 1H), 4.83-4.93 (m,
1H), 4.42-4.54 (m, 1H), 2.48 (s, 3H). D42 F.sub.2HC--H.sub.2C--
2,6-bis-F.sub.3C- 8.51 (d, 1H), 8.39 (d, 1H), 8.14 (d, phenyl- 2H),
7.85 (t, 1H), 6.14-6.44 (m, 1H), 4.49-4.57 (dt, 2H). D43 Et
2,6-bis-F.sub.3C- 8.61 (d, 1H), 8.40 (d, 1H), 8.06 (d, phenyl- 2H),
7.77 (t, 1H), 4.32 (q, 2H), 1.49 (t, 3H). D44 F.sub.2HC--H.sub.2C--
2-I-phenyl- 8.58 (d, 1H), 8.46 (d, 1H), 8.15 (bs, 1H), 8.01-8.03
(d, 1H), 7.61 (dd, 1H), 7.50 (t, 1H), 7.20 (dt, 1H), 6.12-6.42 (m,
1H), 4.80-4.91 (m, 1H), 4.51-4.63 (m, 1H). D45
HC.ident.C--H.sub.2C-- 2,5-di-Cl-6- 8.67 (d, 1H), 8.47 (d, 1H),
7.73 (d, F.sub.3C-phenyl- 1H), 7.68 (d, 1H), 5.00 (d, 2H), 2.29 (t,
1H). D46 Me 2-Cl-5-F.sub.3C- 8.58 (d, 1H), 8.37 (d, 1H), 7.91 (bs,
phenyl- 1H), 7.70 (bs, 2H), 3.70 (s, 3H). D47 Me 2,3,6-tri-Cl- 8.59
(d, 1H), 8.39 (d, 1H), 8.16 (bs, phenyl- 1H), 7.53-7.55 (d, 1H),
7.42-7.45 (d, 1H), 3.70 (s, 3H). D48 Me--C.ident.C--H.sub.2C--
2,5-di-Cl-6- 8.58 (d, 1H), 8.35 (d, 1H), 7.58-7.64 F.sub.3C-phenyl-
(m, 2H), 4.87-4.88 (m, 2H), 1.69-1.70 (m, 3H). D49 Et 2,3-di-Cl-
8.56 (d, 1H), 8.36 (d, 1H), 7.59 (t, phenyl- 2H), 7.34 (t, 1H),
4.32-4.46 (m, 2H), 1.50 (t, 3H). D50 F.sub.2HC--H.sub.2C--
2,3-di-Cl- 8.56 (d, 1H), 8.44 (d, 1H), 7.53-7.61 phenyl- (m, 2H),
7.33 (t, 1H), 6.07-6.37 (tt, 1H), 4.69-4.80 (m, 1H), 4.53-4.65 (m,
1H). D51 F.sub.3C--H.sub.2C-- 2,4-di-Cl- 8.61 (d, 1H), 8.50 (d,
1H), 8.18 (bs, phenyl- 1H), 7.54-7.60 (m, 2H), 7.38-7.41 (m, 1H),
4.87-5.4 (m, 2H). D52 Et 5-Cl-2-F.sub.3C- 8.59 (d, 1H), 8.38 (d,
1H), 8.11 (bs, phenyl- 1H), 7.77 (d, 1H), 7.73 (s, 1H), 7.59- 7.62
(d, 1H), 4.29-4.47 (m, 2H), 1.46 (t, 3H). D53 F.sub.2HC--H.sub.2C--
5-Cl-2-F.sub.3C- 8.61 (d, 1H), 8.47 (d, 1H), 8.14 (bs, phenyl- 1H),
7.77-7.79 (d, 1H), 7.72 (s, 1H), 7.61-7.63 (d, 1H), 6.02-6.35 (m,
1H), 4.82-4.92 (m, 1H), 4.43-4.55 (m, 1H). D54
H.sub.2C.dbd.HC--H.sub.2C-- 5-Cl-2-F.sub.3C- 8.55 (d, 1H), 8.36 (d,
1H), 7.74 (d, phenyl- 1H), 7.71 (s, 1H), 7.58 (d, 1H), 5.96- 6.06
(m, 1H), 5.23-5.40 (m, 2H), 4.81- 4.97 (m, 2H). D55
F.sub.2HC--H.sub.2C-- 2,4-bis-F.sub.3C- d.sub.6-DMSO: 8.57 (d, 1H),
8.53 (d, 1H), phenyl- 8.07-8.10 (m, 2H), 7.74 (d, 1H), 6.12- 6.42
(tt, 1H), 4.36-4.60 (m, 2H). D56 F.sub.2HC--H.sub.2C--
4-Br-2-F.sub.3C- d.sub.6-DMSO: 8.68 (d, 1H), 8.65 (d, 1H), phenyl-
8.03 (d, 1H), 7.99 (dd, 1H), 7.47 (d, 1H), 6.14-6.43 (tt, 1H),
4.41-4.61 (m, 2H). D57 F.sub.2HC--H.sub.2C-- 2,3-di-Cl-6- 8.75 (d,
1H), 8.71 (d, 1H), 8.01 (d, F.sub.3C-phenyl- 1H), 7.88 (d, 1H),
6.18-6.48 (m, 1H), 4.46-4.54 (m, 2H). D58 F.sub.2HC--H.sub.2C--
3-EtO(CO)- 3:1 Mixture of ethyl ester and methyl 6-F.sub.3C- ester.
pyrid-2-yl- Ethyl ester: 8.67 (d, 1H), 8.57 (d, 1H), 7.77 (d, 1H),
7.30 (m, 1H), 5.67-5.91 (m, 1H), 4.65-4.71 (m, 1H), 4.52-4.57 (m,
2H), 4.31-4.39 (m, 1H), 1.49 (t, 3H). Methyl ester: 8.67 (d, 1H),
8.57 (d, 1H), 7.77 (d, 1H), 7.30 (m, 1H), 5.67-5.91 (m, 1H),
4.65-4.71 (m, 1H), 4.31-4.39 (m, 1H), 4.08 (s, 3H). D59
F.sub.2HC--H.sub.2C-- 2-Cl-4-I- 8.55 (d, 1H), 8.41 (d, 1H), 7.91
(s, phenyl- 1H), 7.72 (d, 1H), 7.33 (d, 1H), 6.07-
6.38 (m, 1H), 4.53-4.78 (m, 2H). D60 F.sub.2HC--H.sub.2C--
2-Cl-6-F-5- 8.57 (d, IH), 8.44 (d, 1H), 7.27 (d, MeO- 1H), 7.04 (t,
1H), 6.06-6.36 (m, 1H), phenyl- 4.59-4.77 (m, 2H), 3.90 (s, 3H).
D61 F.sub.2HC--H.sub.2C-- 2-Cl-6-F.sub.3C- Atropisomer A phenyl-
D62 F.sub.2HC--H.sub.2C-- 2-Cl-6-F.sub.3C- Atropisomer B phenyl-
Key: s = singlet; bs = broad singlet; d = doublet; t = triplet; q =
quartet; dd = double doublet; dt = double triplet; tt = triple
triplet; m = multiplet; Me = methyl; Et = ethyl.
TABLE-US-00014 TABLE E Compound of formula (E'), i.e. a compound of
formula (I) wherein R.sup.1 and R.sup.2 are hydrogen, R.sup.5 is
hydroxy, and R.sup.3, R.sup.4 and have the values as described in
the table below. (E') ##STR00062## 1H-NMR (400 MHz, CDCl.sub.3
except Compound where indicated; chemical shifts in No. R.sup.3
R.sup.4 ppm) E1 F.sub.2HC--CH.sub.2-- 2-Cl-5-F.sub.3C- 8.48 (d,
1H), 8.03 (d, 1H), 7.80 (s, phenyl- 1H), 7.68 (d, 2H), 6.03-6.33
(m, 1H), 4.72-4.83 (m, 1H), 4.55-4.67 (m, 1H). E2
F.sub.2HC--CH.sub.2-- 2-Cl-6-F.sub.3C- 8.48 (d, 1H), 8.07 (d, 1H),
7.75-7.79 phenyl- (m, 2H), 7.55-7.59 (m, 1H), 6.01-6.32 (m, 1H),
4.57-4.75 (m, 2H). Key: s = singlet; d = doublet; m =
multiplet.
Biological Examples
[0480] Compound Nos. A5 and A6 of Table A, Compound Nos. B5 and B6
of Table B and Compound No. D46 of Table D were not tested. The
test results of all other compounds are reported below.
Example B1
Herbicidal Action
[0481] Seeds of a variety of test species were sown in sterilized
standard soil in seed trays each having 96 cells. After cultivation
for 8 to 9 days cultivation (post-emergence) under controlled
conditions in a climatic chamber (cultivation at 23/17.degree. C.,
day/night; 13 hours light; 50-60% humidity), the plants were
treated with an aqueous spray solution of 1000 mg/l of the active
ingredient dissolved in 10% DMSO (dimethyl sulfoxide, CAS RN
67-68-5) as a solvent, equivalent to 1000 g/ha. The plants were
grown in the climatic chamber after application at (24/19.degree.
C., day/night; 13 hours light; 50-60% humidity) and watered twice
daily. After 9 days until the test was evaluated (10=total damage
to plant, 0=no damage to plant)
TABLE-US-00015 TABLE B1 Application post-emergence Comp No. Rate
(g/ha) STEME NAAOF AMARE SOLNI B1 1000 0 0 0 2 B3 1000 0 0 0 2 C1
1000 6 4 0 3 C2 1000 6 4 3 0 C3 1000 2 2 1 3 C4 1000 8 6 7 5 C5
1000 7 8 5 1 C6 1000 8 8 0 7 C7 1000 8 8 3 7 C8 1000 0 0 2 7 C9
1000 6 6 7 4 C40 1000 1 0 0 0 C41 1000 4 8 0 0 D1 1000 8 7 0 0 D2
1000 7 7 7 7 STEME = Stellaria media; NAAOF = Nasturtium
officinale; AMARE = Amaranthus retroflexus; SOLNI = Solanum
nigrum.
[0482] Compound Nos. A1 to A4 of Table A, Compound Nos. B2 and B4
of Table B were tested using the same protocols and showed little
or no damage to the test plants under the test conditions.
Example B2
Herbicidal Action
[0483] Seeds of a variety of test species were sown in standard
soil in pots. After 8 days cultivation (post-emergence) under
controlled conditions in a glasshouse (at 24/16.degree. C.,
day/night; 14 hours light; 65% humidity), the plants were sprayed
with an aqueous spray solution derived from the formulation of the
technical active ingredient in acetone/water (50:50) solution
containing 0.5% Tween 20 (polyoxyethelyene sorbitan monolaurate,
CAS RN 9005-64-5). The test plants were then grown in a glasshouse
under controlled conditions in a glasshouse (at 24/16.degree. C.,
day/night; 14 hours light; 65% humidity) and watered twice daily.
After 13 days, the test was evaluated (10=total damage to plant;
0=no damage to plant).
TABLE-US-00016 TABLE B2 Application post-emergence Rate Comp No.
(g/ha) SOLNI AMARE SETFA ECHCG IPOHE C11 1000 6 1 4 3 2 C13 1000 9
10 3 10 10 C15 1000 9 9 2 7 8 C16 1000 10 7 0 3 7 C17 1000 9 8 4 5
7 C18 1000 3 9 0 1 6 C19 1000 6 9 0 4 8 C20 1000 10 10 0 8 10 C21
1000 10 7 4 6 9 C22 1000 10 10 4 7 9 C23 1000 6 5 3 4 4 C24 1000 9
2 0 4 9 C25 1000 10 9 0 6 9 C26 1000 0 9 0 0 0 C27 1000 9 7 6 3 6
C28 1000 6 7 2 2 6 C29 1000 5 2 0 4 5 C30 1000 10 8 5 6 9 C31 1000
9 8 7 8 8 C32 1000 8 8 1 7 9 C33 1000 6 1 0 0 5 C34 1000 9 7 2 7 10
C35 1000 10 10 7 7 10 C36 1000 9 9 3 7 10 C37 1000 9 8 6 8 9 C38
1000 10 9 9 9 10 C39 1000 10 9 4 4 9 C42 1000 3 2 2 2 4 C43 1000 6
5 3 5 5 C44 1000 10 10 6 9 10 C45 1000 7 0 1 4 9 C46 1000 6 4 0 4 5
C47 1000 10 10 7 4 7 C48 1000 5 3 0 0 6 C49 1000 9 9 6 8 9 C50 1000
6 5 4 5 7 C51 1000 7 5 0 1 6 C52 1000 8 9 8 7 10 C53 1000 5 8 5 8 4
C54 1000 8 6 2 3 8 C55 1000 7 7 2 2 8 C56 1000 2 10 0 0 0 C57 1000
10 10 3 4 10 C58 1000 9 10 4 6 9 C59 1000 10 10 3 7 10 C60 1000 10
10 1 7 10 C61 1000 10 10 10 9 10 C62 1000 6 7 6 4 8 C63 1000 9 9 7
7 10 C64 1000 5 4 3 5 6 C65 1000 2 2 2 0 1 C67 1000 1 0 0 0 2 C68
1000 2 0 0 0 1 C69 1000 6 4 0 2 7 C70 1000 8 7 1 7 10 C71 1000 9 8
1 6 10 C72 1000 10 9 1 6 10 C73 1000 7 7 2 2 7 C74 1000 6 7 3 4 7
C75 1000 6 5 0 1 2 C76 1000 3 0 0 0 0 C77 1000 10 10 9 9 10 C78
1000 6 4 3 4 3 C79 1000 9 9 6 7 9 C80 1000 10 10 0 6 10 C81 1000 10
10 7 8 10 C82 1000 10 10 8 9 10 C83 1000 10 9 1 7 10 C84 1000 10 9
7 7 8 C85 1000 10 7 6 7 9 C86 1000 6 5 2 5 4 C87 1000 10 7 0 5 9
C88 1000 9 9 4 6 9 C89 1000 10 7 1 6 9 C90 1000 10 8 1 2 9 C91 1000
9 9 3 6 10 C92 1000 9 6 3 4 9 C93 1000 6 0 0 3 6 C94 1000 9 6 2 6 9
C95 1000 9 7 3 6 10 C96 1000 7 0 0 1 4 C97 1000 6 0 0 1 4 C98 1000
3 0 0 0 0 C99 1000 8 3 1 2 3 C100 1000 9 4 2 2 6 C101 1000 10 4 2 5
8 C102 1000 7 1 0 0 6 C103 1000 9 8 6 7 6 C104 1000 10 10 3 6 9
C105 1000 9 10 9 9 8 C106 1000 7 6 0 1 3 C107 1000 7 5 3 5 6 C108
1000 7 4 2 3 3 C109 1000 8 5 2 5 9 C110 1000 8 9 4 5 8 C111 1000 9
8 6 6 9 C112 1000 10 10 6 6 9 C113 1000 10 8 6 7 9 C114 1000 10 4 2
0 6 C115 1000 9 8 5 1 6 C116 1000 10 10 3 2 6 C117 1000 10 10 7 8 9
C118 1000 8 6 4 5 4 C119 1000 6 3 3 5 3 C120 1000 9 9 9 8 10 C121
1000 5 0 2 0 1 C122 1000 9 5 3 2 6 C123 1000 10 4 1 2 4 C124 1000 2
10 0 0 2 C125 1000 9 9 8 8 8 C126 1000 9 9 4 7 7 C127 1000 10 8 2 4
8 C128 1000 9 7 0 0 8 C129 1000 10 10 9 9 9 C130 1000 10 10 7 8 10
C131 1000 10 9 2 4 9 C132 1000 10 10 7 6 10 C133 1000 10 10 7 8 8
C134 1000 8 8 4 5 3 C135 1000 10 8 10 7 8 C136 1000 8 3 2 0 7 C137
1000 9 7 8 3 8 C138 1000 7 0 0 1 2 C139 1000 0 0 3 0 1 C140 1000 2
0 0 0 2 C141 1000 8 7 0 2 7 C142 1000 6 4 0 1 3 C143 1000 10 1 0 4
8 C144 1000 4 0 0 0 7 C145 1000 8 0 2 5 8 C146 1000 7 8 2 4 9 C147
1000 9 1 3 2 9 C148 1000 9 7 2 3 8 C149 1000 8 10 0 0 0 D3 1000 1
10 0 1 1 D4 1000 10 8 2 4 10 D5 1000 10 10 6 4 9 D6 1000 10 10 5 7
9 D7 1000 5 9 0 0 3 D8 1000 2 9 0 0 0 D9 1000 10 9 2 4 10 D10 1000
10 9 2 4 9 D11 1000 10 10 8 8 9 D12 1000 9 6 2 0 5 D13 1000 9 8 2 5
9 D14 1000 9 9 5 7 9 D15 1000 9 9 4 2 9 D16 1000 10 10 2 5 9 D17
1000 10 10 9 9 10 D18 1000 10 10 5 4 10 D19 1000 2 0 0 0 0 D20 1000
5 3 1 1 6 D21 1000 9 8 6 6 9 D22 1000 10 10 6 7 10 D23 1000 8 8 2 2
9 D24 1000 10 6 1 3 10 D25 1000 10 10 4 3 9 D26 1000 8 8 4 7 8 D27
1000 8 9 8 7 7 D28 1000 9 10 8 8 8 D29 1000 7 5 3 2 7 D30 1000 10
10 3 6 10 D31 1000 10 10 9 9 10 D32 1000 6 5 1 0 5 D33 1000 10 9 8
8 10 D34 1000 1 0 1 0 2 D35 1000 9 8 4 1 10 D36 1000 10 10 2 6 10
D37 1000 9 10 5 3 10 D38 1000 8 9 0 1 5 D39 1000 9 10 9 9 10 D41
1000 10 9 2 1 9 D42 1000 8 7 7 4 9 D43 1000 8 7 4 3 8 D44 1000 10
10 6 9 10 D45 1000 9 8 6 6 8 D47 1000 10 8 1 4 8 D48 1000 8 3 0 0 7
D49 1000 8 4 1 1 6 D50 1000 10 5 2 1 8 D51 1000 8 7 1 2 7 D52 1000
7 5 4 4 5 D53 1000 10 8 6 6 7 D54 1000 7 2 3 3 4 D55 1000 10 10 4 5
10 D56 1000 9 10 6 7 10 D57 1000 10 10 10 9 7 D59 1000 8 4 1 3 4
D60 1000 7 1 2 4 8 E1 1000 9 4 1 3 7 E2 1000 9 8 8 6 8 SOLNI =
Solanum nigrum; AMARE = Amaranthus retroflexus; SETFA = Setaria
faberi; ECHCG = Echinochloa crus-galli; IPOHE = Ipomea
hederaceae.
[0484] Compound Nos. C10, C14 and C66 of Table C and Compound Nos.
D40 and D58 of Table D were tested using the same protocols and
showed little or no damage to the test plants under the test
conditions.
Example B3
Herbicidal Action
[0485] Seeds of a variety of test species were sown in sterilized
compost in small pots. After cultivation for seven days
(post-emergence) in controlled conditions in the glasshouse (at
24/16.degree. C., day/night; 14 hours light; 65% humidity) the
plants were sprayed with 1 mg of the active ingredient, formulated
in 2.5 ml acetone/water (50:50) solution, which is equivalent to
1000 g/ha. Once the foliage was dry, the pots were kept in the
glasshouse (at 24/16.degree. C., day/night; 14 hours light; 65%
humidity), and were watered twice daily. After 13 days the test was
evaluated (10=total damage to plant, 0=no damage to plant).
TABLE-US-00017 TABLE B3 Application post-emergence Comp No. Rate
(g/ha) AMARE ALOMY DIGSA CHEAL C12 1000 -- 6 -- 9 AMARE =
Amaranthus retroflexus; ALOMY = Alopecurus myosuroides; DIGSA =
Digitaria sanguinalis; CHEAL = Chenopodium album.
* * * * *
References